Link Between Antibiotic Persistence and Antibiotic Resistance in Bacterial Pathogens

Wolfgang Eisenreich, Thomas Rudel, Jürgen Heesemann, Werner Goebel, Wolfgang Eisenreich, Thomas Rudel, Jürgen Heesemann, Werner Goebel

Abstract

Both, antibiotic persistence and antibiotic resistance characterize phenotypes of survival in which a bacterial cell becomes insensitive to one (or even) more antibiotic(s). However, the molecular basis for these two antibiotic-tolerant phenotypes is fundamentally different. Whereas antibiotic resistance is genetically determined and hence represents a rather stable phenotype, antibiotic persistence marks a transient physiological state triggered by various stress-inducing conditions that switches back to the original antibiotic sensitive state once the environmental situation improves. The molecular basics of antibiotic resistance are in principle well understood. This is not the case for antibiotic persistence. Under all culture conditions, there is a stochastically formed, subpopulation of persister cells in bacterial populations, the size of which depends on the culture conditions. The proportion of persisters in a bacterial population increases under different stress conditions, including treatment with bactericidal antibiotics (BCAs). Various models have been proposed to explain the formation of persistence in bacteria. We recently hypothesized that all physiological culture conditions leading to persistence converge in the inability of the bacteria to re-initiate a new round of DNA replication caused by an insufficient level of the initiator complex ATP-DnaA and hence by the lack of formation of a functional orisome. Here, we extend this hypothesis by proposing that in this persistence state the bacteria become more susceptible to mutation-based antibiotic resistance provided they are equipped with error-prone DNA repair functions. This is - in our opinion - in particular the case when such bacterial populations are exposed to BCAs.

Keywords: ATP-DnaA complex; DNA replication initiation; bacterial pathogens; persistence; resistance.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Eisenreich, Rudel, Heesemann and Goebel.

Figures

Figure 1
Figure 1
Formation of the antibiotic-tolerant persistence state (according to our hypothesis). (A) Different stress-induced physiological conditions (including treatment with BCAs) lead to increased production of reactive oxygen species (ROS) that damage cell components including DNA, to reduced energy production that inhibits DNA replication and repair, and to reduced metabolic activities. (B) Replicating DNA is particularly sensitive to irreparable damage (especially double strand breaks) which leads to killing of the bacteria (a). Cells with terminated chromosomal DNA replication but unable to re-initiate replication (due to the lack of sufficient ATP-DnaA initiator complex – see text for details) have closed circular supercoiled (ccs) DNA that is rather insensitive to lethal DNA damage (b). According to our hypothesis, this cellular state arrested in the termination of DNA replication represents the state of persistence (c). Solid blue circle, parental chromosomal DNA; dashed blue circle, replicating DNA; dashed green vertical line, beginning of cell division; ccs, closed circular supercoiled DNA in the terminated state; oriC, origin of replication marked by the red triangle; BCAs, bactericidal antibiotics.
Figure 2
Figure 2
Emergence of mutation-based ABR in persisters. Treatment of a bacterial population with BCAs leads to killing of the majority of the bacterial cells that are in an active DNA replication phase and to the generation of persisters with terminated DNA replication (see Figure 2 and text for details). The ccs chromosomal DNA of the persisters may contain non-lethal DNA damages (green bars) that can be repaired mainly by error-prone DNA repair processes, e.g. by TLS DNA polymerases, however at the expense of increased mutation rates that lead – among others – to ABR mutants.

References

    1. Acosta S., Carela M., Garcia-Gonzalez A., Gines M., Vicens L., Cruet R., et al. . (2015). DNA Repair is Associated With Information Content in Bacteria, Archaea, and DNA Viruses. J. Hered. 106, 644–659. doi: 10.1093/jhered/esv055
    1. Ailloud F., Estibariz I., Suerbaum S. (2021). Evolved to Vary: Genome and Epigenome Variation in the Human Pathogen Helicobacter Pylori . FEMS Microbiol. Rev. 45. doi: 10.1093/femsre/fuaa042
    1. Akporiaye E. T., Rowatt J. D., Aragon A. A., Baca O. G. (1983). Lysosomal Response of a Murine Macrophage-Like Cell Line Persistently Infected With Coxiella Burnetii . Infect. Immun. 40, 1155–1162. doi: 10.1128/iai.40.3.1155-1162.1983
    1. Aldred K. J., Kerns R. J., Osheroff N. (2014). Mechanism of Quinolone Action and Resistance. Biochemistry 53, 1565–1574. doi: 10.1021/bi5000564
    1. Alekshun M. N., Levy S. B. (2007). Molecular Mechanisms of Antibacterial Multidrug Resistance. Cell 128, 1037–1050. doi: 10.1016/j.cell.2007.03.004
    1. Allen H. K., Donato J., Wang H. H., Cloud-Hansen K. A., Davies J., Handelsman J. (2010). Call of the Wild: Antibiotic Resistance Genes in Natural Environments. Nat. Rev. Microbiol. 8, 251–259. doi: 10.1038/nrmicro2312
    1. Almahmoud I., Kay E., Schneider D., Maurin M. (2009). Mutational Paths Towards Increased Fluoroquinolone Resistance in Legionella Pneumophila . J. Antimicrob. Chemother. 64, 284–293. doi: 10.1093/jac/dkp173
    1. Al Mamun A., Kishida K., Christie P. J. (2021). Protein Transfer Through an F Plasmid-Encoded Type IV Secretion System Suppresses the Mating-Induced SOS Response. mBio 12, e0162921. doi: 10.1128/mBio.01629-21
    1. Amato S. M., Brynildsen M. P. (2015). Persister Heterogeneity Arising From a Single Metabolic Stress. Curr. Biol. 25, 2090–2098. doi: 10.1016/j.cub.2015.06.034
    1. Amato S. M., Fazen C. H., Henry T. C., Mok W. W., Orman M. A., Sandvik E. L., et al. . (2014). The Role of Metabolism in Bacterial Persistence. Front. Microbiol. 5, 70. doi: 10.3389/fmicb.2014.00070
    1. Amato S. M., Orman M. A., Brynildsen M. P. (2013). Metabolic Control of Persister Formation in Escherichia Coli . Mol. Cell 50, 475–487. doi: 10.1016/j.molcel.2013.04.002
    1. Aminov R. I., Mackie R. I. (2007). Evolution and Ecology of Antibiotic Resistance Genes. FEMS Microbiol. Lett. 271, 147–161. doi: 10.1111/j.1574-6968.2007.00757.x
    1. Andersson D. I., Nicoloff H., Hjort K. (2019). Mechanisms and Clinical Relevance of Bacterial Heteroresistance. Nat. Rev. Microbiol. 17, 479–496. doi: 10.1038/s41579-019-0218-1
    1. Aranda J., Lopez M., Leiva E., Magan A., Adler B., Bou G., et al. . (2014). Role of Acinetobacter Baumannii UmuD Homologs in Antibiotic Resistance Acquired Through DNA Damage-Induced Mutagenesis. Antimicrob. Agents Chemother. 58, 1771–1773. doi: 10.1128/AAC.02346-13
    1. Ayrapetyan M., Williams T., Oliver J. D. (2018). Relationship Between the Viable But Nonculturable State and Antibiotic Persister Cells. J. Bacteriol. 200, e00249. doi: 10.1128/JB.00249-18
    1. Babakhani S., Oloomi M. (2018). Transposons: The Agents of Antibiotic Resistance in Bacteria. J. Basic Microbiol. 58, 905–917. doi: 10.1002/jobm.201800204
    1. Babin B. M., Atangcho L., Van Eldijk M. B., Sweredoski M. J., Moradian A., Hess S., et al. . (2017). Selective Proteomic Analysis of Antibiotic-Tolerant Cellular Subpopulations in Pseudomonas Aeruginosa Biofilms. mBio 8. doi: 10.1128/mBio.01593-17
    1. Baharoglu Z., Babosan A., Mazel D. (2014). Identification of Genes Involved in Low Aminoglycoside-Induced SOS Response in Vibrio Cholerae: A Role for Transcription Stalling and Mfd Helicase. Nucleic Acids Res. 42, 2366–2379. doi: 10.1093/nar/gkt1259
    1. Baharoglu Z., Bikard D., Mazel D. (2010). Conjugative DNA Transfer Induces the Bacterial SOS Response and Promotes Antibiotic Resistance Development Through Integron Activation. PloS Genet. 6, e1001165. doi: 10.1371/journal.pgen.1001165
    1. Baharoglu Z., Krin E., Mazel D. (2012). Connecting Environment and Genome Plasticity in the Characterization of Transformation-Induced SOS Regulation and Carbon Catabolite Control of the Vibrio Cholerae Integron Integrase. J. Bacteriol. 194, 1659–1667. doi: 10.1128/JB.05982-11
    1. Baharoglu Z., Krin E., Mazel D. (2013). RpoS Plays a Central Role in the SOS Induction by Sub-Lethal Aminoglycoside Concentrations in Vibrio Cholerae . PloS Genet. 9, e1003421. doi: 10.1371/journal.pgen.1003421
    1. Baharoglu Z., Mazel D. (2014). SOS, the Formidable Strategy of Bacteria Against Aggressions. FEMS Microbiol. Rev. 38, 1126–1145. doi: 10.1111/1574-6976.12077
    1. Baker K. S., Dallman T. J., Field N., Childs T., Mitchell H., Day M., et al. . (2018). Horizontal Antimicrobial Resistance Transfer Drives Epidemics of Multiple Shigella Species. Nat. Commun. 9, 1462. doi: 10.1038/s41467-018-03949-8
    1. Bakkeren E., Diard M., Hardt W. D. (2020). Evolutionary Causes and Consequences of Bacterial Antibiotic Persistence. Nat. Rev. Microbiol. 18, 479–490. doi: 10.1038/s41579-020-0378-z
    1. Bakkeren E., Huisman J. S., Fattinger S. A., Hausmann A., Furter M., Egli A., et al. . (2019). Salmonella Persisters Promote the Spread of Antibiotic Resistance Plasmids in the Gut. Nature 573, 276–280. doi: 10.1038/s41586-019-1521-8
    1. Balaban N. Q., Gerdes K., Lewis K., Mckinney J. D. (2013). A Problem of Persistence: Still More Questions Than Answers? Nat. Rev. Microbiol. 11, 587–591. doi: 10.1038/nrmicro3076
    1. Balaban N. Q., Helaine S., Lewis K., Ackermann M., Aldridge B., Andersson D. I., et al. . (2019). Definitions and Guidelines for Research on Antibiotic Persistence. Nat. Rev. Microbiol. 17, 441–448. doi: 10.1038/s41579-019-0196-3
    1. Band V. I., Weiss D. S. (2019). Heteroresistance: A Cause of Unexplained Antibiotic Treatment Failure? PloS Pathog. 15, e1007726. doi: 10.1371/journal.ppat.1007726
    1. Baquero F., Lanza V. F., Duval M., Coque T. M. (2020). Ecogenetics of Antibiotic Resistance in Listeria Monocytogenes . Mol. Microbiol. 113, 570–579. doi: 10.1111/mmi.14454
    1. Baquero F., Levin B. R. (2021). Proximate and Ultimate Causes of the Bactericidal Action of Antibiotics. Nat. Rev. Microbiol. 19, 123–132. doi: 10.1038/s41579-020-00443-1
    1. Beaber J. W., Hochhut B., Waldor M. K. (2004). SOS Response Promotes Horizontal Dissemination of Antibiotic Resistance Genes. Nature 427, 72–74. doi: 10.1038/nature02241
    1. Bearson B. L., Brunelle B. W. (2015). Fluoroquinolone Induction of Phage-Mediated Gene Transfer in Multidrug-Resistant Salmonella . Int. J. Antimicrob. Agents 46, 201–204. doi: 10.1016/j.ijantimicag.2015.04.008
    1. Beatty W. L., Morrison R. P., Byrne G. I. (1995). Reactivation of Persistent Chlamydia Trachomatis Infection in Cell Culture. Infect. Immun. 63, 199–205. doi: 10.1128/iai.63.1.199-205.1995
    1. Behzadi P., Garcia-Perdomo H. A., Karpinski T. M., Issakhanian L. (2020). Metallo-Ss-Lactamases: A Review. Mol. Biol. Rep. 47, 6281–6294. doi: 10.1007/s11033-020-05651-9
    1. Belenky P., Ye J. D., Porter C. B., Cohen N. R., Lobritz M. A., Ferrante T., et al. . (2015). Bactericidal Antibiotics Induce Toxic Metabolic Perturbations That Lead to Cellular Damage. Cell Rep. 13, 968–980. doi: 10.1016/j.celrep.2015.09.059
    1. Beuls E., Modrie P., Deserranno C., Mahillon J. (2012). High-Salt Stress Conditions Increase the Paw63 Transfer Frequency in Bacillus Thuringiensis . Appl. Environ. Microbiol. 78, 7128–7131. doi: 10.1128/AEM.01105-12
    1. Bigger J. W. (1944). Treatment of Staphylococcal Infections With Penicillin by Intermittent Sterilisation. Lancet 244, 497–500. doi: 10.1016/S0140-6736(00)74210-3
    1. Binet R., Maurelli A. T. (2005). Frequency of Spontaneous Mutations That Confer Antibiotic Resistance in Chlamydia . Antimicrob. Agents Chemother. spp49, 2865–2873. doi: 10.1128/AAC.49.7.2865-2873.2005
    1. Biswas S., Raoult D., Rolain J. M. (2006). Molecular Characterization of Resistance to Macrolides in Bartonella Henselae . Antimicrob. Agents Chemother. 50, 3192–3193. doi: 10.1128/AAC.00263-06
    1. Blair J. M. A., Webber M. A., Baylay A. J., Ogbolu D. O., Piddock L. J. (2015). Molecular Mechanisms of Antibiotic Resistance. Nat. Rev. Microbiol. 13, 42–51. doi: 10.1038/nrmicro3380
    1. Blanchard J. L., Wholey W. Y., Conlon E. M., Pomposiello P. J. (2007). Rapid Changes in Gene Expression Dynamics in Response to Superoxide Reveal SoxRS-Dependent and Independent Transcriptional Networks. PloS One 2, e1186. doi: 10.1371/journal.pone.0001186
    1. Blazquez J., Rodriguez-Beltran J., Matic I. (2018). Antibiotic-Induced Genetic Variation: How it Arises and How it can be Prevented. Annu. Rev. Microbiol. 72, 209–230. doi: 10.1146/annurev-micro-090817-062139
    1. Blokesch M. (2016). Natural Competence for Transformation. Curr. Biol. 26, R1126–R1130. doi: 10.1016/j.cub.2016.11.023
    1. Bolard A., Plesiat P., Jeannot K. (2018). Mutations in Gene Fusa1 as a Novel Mechanism of Aminoglycoside Resistance in Clinical Strains of Pseudomonas Aeruginosa . Antimicrob. Agents Chemother. 62. doi: 10.1128/AAC.01835-17
    1. Bollen C., Dewachter L., Michiels J. (2021). Protein Aggregation as a Bacterial Strategy to Survive Antibiotic Treatment. Front. Mol. Biosci. 8, 669664. doi: 10.3389/fmolb.2021.669664
    1. Bolotin E., Hershberg R. (2015). Gene Loss Dominates as a Source of Genetic Variation Within Clonal Pathogenic Bacterial Species. Genome Biol. Evol. 7, 2173–2187. doi: 10.1093/gbe/evv135
    1. Bordenstein S. R., Reznikoff W. S. (2005). Mobile DNA in Obligate Intracellular Bacteria. Nat. Rev. Microbiol. 3, 688–699. doi: 10.1038/nrmicro1233
    1. Borel N., Leonard C., Slade J., Schoborg R. V. (2016). Chlamydial Antibiotic Resistance and Treatment Failure in Veterinary and Human Medicine. Curr. Clin. Microbiol. Rep. 3, 10–18. doi: 10.1007/s40588-016-0028-4
    1. Bradford P. A. (2001). Extended-Spectrum Beta-Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat. Clin. Microbiol. Rev. 14, 933–951. doi: 10.1128/CMR.14.4.933-951.2001
    1. Brennan R. E., Russell K., Zhang G., Samuel J. E. (2004). Both Inducible Nitric Oxide Synthase and NADPH Oxidase Contribute to the Control of Virulent Phase I Coxiella Burnetii Infections. Infect. Immun. 72, 6666–6675. doi: 10.1128/IAI.72.11.6666-6675.2004
    1. Bunnell B. E., Escobar J. F., Bair K. L., Sutton M. D., Crane J. K. (2017). Zinc Blocks SOS-Induced Antibiotic Resistance via Inhibition of RecA in Escherichia Coli . PloS One 12, e0178303. doi: 10.1371/journal.pone.0178303
    1. Burmeister A. R. (2015). Horizontal Gene Transfer. Evol. Med. Public Health 2015, 193–194. doi: 10.1093/emph/eov018
    1. Bush N. G., Diez-Santos I., Abbott L. R., Maxwell A. (2020). Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance. Molecules 25. doi: 10.3390/molecules25235662
    1. Cabiscol E., Tamarit J., Ros J. (2000). Oxidative Stress in Bacteria and Protein Damage by Reactive Oxygen Species. Int. Microbiol. 3, 3–8.
    1. Cabral D. J., Wurster J. I., Belenky P. (2018). Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions. Pharm. (Basel) 11. doi: 10.3390/ph11010014
    1. Caspar Y., Maurin M. (2017). Francisella Tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In Vitro and in Animal Models. Front. Cell Infect. Microbiol. 7, 122. doi: 10.3389/fcimb.2017.00122
    1. Cerchiaro G., Bolin C., Cardozo-Pelaez F. (2009). Hydroxyl Radical Oxidation of Guanosine 5'-Triphosphate (GTP): Requirement for a GTP-Cu(II) Complex. Redox Rep. 14, 82–92. doi: 10.1179/135100009X392520
    1. Chakarov S., Petkova R., Russev G. C., Zhelev N. (2014). DNA Repair and Carcinogenesis. BioDiscovery 12. doi: 10.7750/BioDiscovery.2014.12.1
    1. Charbon G., Mendoza-Chamizo B., Campion C., Li X., Jensen P. R., Frimodt-Moller J., et al. . (2021). Energy Starvation Induces a Cell Cycle Arrest in Escherichia Coli by Triggering Degradation of the DnaA Initiator Protein. Front. Mol. Biosci. 8, 629953. doi: 10.3389/fmolb.2021.629953
    1. Charpentier E., Courvalin P. (1999). Antibiotic Resistance in Listeria . Antimicrob. Agents Chemother. spp43, 2103–2108. doi: 10.1128/AAC.43.9.2103
    1. Charpentier X., Kay E., Schneider D., Shuman H. A. (2011). Antibiotics and UV Radiation Induce Competence for Natural Transformation in Legionella Pneumophila . J. Bacteriol. 193, 1114–1121. doi: 10.1128/JB.01146-10
    1. Chatterjee N., Walker G. C. (2017). Mechanisms of DNA Damage, Repair, and Mutagenesis. Environ. Mol. Mutagen. 58, 235–263. doi: 10.1002/em.22087
    1. Chen J., Novick R. P. (2009). Phage-Mediated Intergeneric Transfer of Toxin Genes. Science 323, 139–141. doi: 10.1126/science.1164783
    1. Cheverton A. M., Gollan B., Przydacz M., Wong C. T., Mylona A., Hare S. A., et al. . (2016). A Salmonella Toxin Promotes Persister Formation Through Acetylation of tRNA. Mol. Cell 63, 86–96. doi: 10.1016/j.molcel.2016.05.002
    1. Christman M. F., Storz G., Ames B. N. (1989). OxyR, a Positive Regulator of Hydrogen Peroxide-Inducible Genes in Escherichia Coli and Salmonella Typhimurium, is Homologous to a Family of Bacterial Regulatory Proteins. Proc. Natl. Acad. Sci. U.S.A. 86, 3484–3488. doi: 10.1073/pnas.86.10.3484
    1. Claverys J. P., Prudhomme M., Martin B. (2006). Induction of Competence Regulons as a General Response to Stress in Gram-Positive Bacteria. Annu. Rev. Microbiol. 60, 451–475. doi: 10.1146/annurev.micro.60.080805.142139
    1. Cohen N. R., Lobritz M. A., Collins J. J. (2013). Microbial Persistence and the Road to Drug Resistance. Cell Host Microbe 13, 632–642. doi: 10.1016/j.chom.2013.05.009
    1. Colque C. A., Albarracin Orio A. G., Feliziani S., Marvig R. L., Tobares A. R., Johansen H. K., et al. . (2020). Hypermutator Pseudomonas Aeruginosa Exploits Multiple Genetic Pathways to Develop Multidrug Resistance During Long-Term Infections in the Airways of Cystic Fibrosis Patients. Antimicrob. Agents Chemother. 64. doi: 10.1128/AAC.02142-19
    1. Cox M. M. (2003). The Bacterial RecA Protein as a Motor Protein. Annu. Rev. Microbiol. 57, 551–577. doi: 10.1146/annurev.micro.57.030502.090953
    1. Cox G., Ejim L., Stogios P. J., Koteva K., Bordeleau E., Evdokimova E., et al. . (2018). Plazomicin Retains Antibiotic Activity Against Most Aminoglycoside Modifying Enzymes. ACS Infect. Dis. 4, 980–987. doi: 10.1021/acsinfecdis.8b00001
    1. Cui P., Niu H., Shi W., Zhang S., Zhang W., Zhang Y. (2018). Identification of Genes Involved in Bacteriostatic Antibiotic-Induced Persister Formation. Front. Microbiol. 9, 413. doi: 10.3389/fmicb.2018.00413
    1. Cuypers W. L., Jacobs J., Wong V., Klemm E. J., Deborggraeve S., Van Puyvelde S. (2018). Fluoroquinolone Resistance in Salmonella: Insights by Whole-Genome Sequencing. Microb. Genom. 4. doi: 10.1099/mgen.0.000195
    1. Davies J. (1994). Inactivation of Antibiotics and the Dissemination of Resistance Genes. Science 264, 375–382. doi: 10.1126/science.8153624
    1. Davies J. E. (1997). Origins, Acquisition and Dissemination of Antibiotic Resistance Determinants. Ciba. Found. Symp. 207, 15–27.
    1. Decousser J. W., Poirel L., Nordmann P. (2017). Recent Advances in Biochemical and Molecular Diagnostics for the Rapid Detection of Antibiotic-Resistant Enterobacteriaceae: A Focus on Ss-Lactam Resistance. Expert Rev. Mol. Diagn. 17, 327–350. doi: 10.1080/14737159.2017.1289087
    1. Defraine V., Fauvart M., Michiels J. (2018). Fighting Bacterial Persistence: Current and Emerging Anti-Persister Strategies and Therapeutics. Drug Resist. Update 38, 12–26. doi: 10.1016/j.drup.2018.03.002
    1. Deguchi T., Hatazaki K., Ito S., Kondo H., Horie K., Nakane K., et al. . (2018). Macrolide and Fluoroquinolone Resistance is Uncommon in Clinical Strains of Chlamydia Trachomatis . J. Infect. Chemother. 24, 610–614. doi: 10.1016/j.jiac.2018.03.007
    1. Demain A. L., Fang A. (2000). The Natural Functions of Secondary Metabolites. Adv. Biochem. Eng. Biotechnol. 69, 1–39. doi: 10.1007/3-540-44964-7_1
    1. Demple B., Harrison L. (1994). Repair of Oxidative Damage to DNA: Enzymology and Biology. Annu. Rev. Biochem. 63, 915–948. doi: 10.1146/annurev.bi.63.070194.004411
    1. Dewachter L., Fauvart M., Michiels J. (2019). Bacterial Heterogeneity and Antibiotic Survival: Understanding and Combatting Persistence and Heteroresistance. Mol. Cell 76, 255–267. doi: 10.1016/j.molcel.2019.09.028
    1. Domenech A., Brochado A. R., Sender V., Hentrich K., Henriques-Normark B., Typas A., et al. . (2020). Proton Motive Force Disruptors Block Bacterial Competence and Horizontal Gene Transfer. Cell Host Microbe 27, 544–555 e543. doi: 10.1016/j.chom.2020.02.002
    1. Domingues S., Nielsen K. M., Da Silva G. J. (2012). Various Pathways Leading to the Acquisition of Antibiotic Resistance by Natural Transformation. Mob. Genet. Elements 2, 257–260. doi: 10.4161/mge.23089
    1. Dorer M. S., Fero J., Salama N. R. (2010). DNA Damage Triggers Genetic Exchange in Helicobacter Pylori . PloS Pathog. 6, e1001026. doi: 10.1371/journal.ppat.1001026
    1. Dörr T., Lewis K., Vulic M. (2009). SOS Response Induces Persistence to Fluoroquinolones in Escherichia Coli . PloS Genet. 5, e1000760. doi: 10.1371/journal.pgen.1000760
    1. Dörr T., Vulic M., Lewis K. (2010). Ciprofloxacin Causes Persister Formation by Inducing the TisB Toxin in Escherichia Coli . PloS Biol. 8, e1000317. doi: 10.1371/journal.pbio.1000317
    1. Drlica K., Zhao X. (1997). DNA Gyrase, Topoisomerase IV, and the 4-Quinolones. Microbiol. Mol. Biol. Rev. 61, 377–392. doi: 10.1128/mmbr.61.3.377-392
    1. Droge W. (2002). Free Radicals in the Physiological Control of Cell Function. Physiol. Rev. 82, 47–95. doi: 10.1152/physrev.00018.2001
    1. Dupre-Crochet S., Erard M., Nubetae O. (2013). ROS Production in Phagocytes: Why, When, and Where? J. Leukoc. Biol. 94, 657–670. doi: 10.1189/jlb.1012544
    1. Dwyer D. J., Collins J. J., Walker G. C. (2015). Unraveling the Physiological Complexities of Antibiotic Lethality. Annu. Rev. Pharmacol. Toxicol. 55, 313–332. doi: 10.1146/annurev-pharmtox-010814-124712
    1. Dwyer D. J., Kohanski M. A., Hayete B., Collins J. J. (2007). Gyrase Inhibitors Induce an Oxidative Damage Cellular Death Pathway in Escherichia Coli . Mol. Syst. Biol. 3, 91. doi: 10.1038/msb4100135
    1. Eisenreich W., Heesemann J., Rudel T., Goebel W. (2015). Metabolic Adaptations of Intracellullar Bacterial Pathogens and Their Mammalian Host Cells During Infection ("Pathometabolism"). Microbiol. Spectr. 3. doi: 10.1128/9781555818883.ch3
    1. Eisenreich W., Rudel T., Heesemann J., Goebel W. (2017). To Eat and to be Eaten: Mutual Metabolic Adaptations of Immune Cells and Intracellular Bacterial Pathogens Upon Infection. Front. Cell Infect. Microbiol. 7, 316. doi: 10.3389/fcimb.2017.00316
    1. Eisenreich W., Rudel T., Heesemann J., Goebel W. (2019). How Viral and Intracellular Bacterial Pathogens Reprogram the Metabolism of Host Cells to Allow Their Intracellular Replication. Front. Cell Infect. Microbiol. 9, 42. doi: 10.3389/fcimb.2019.00042
    1. Eisenreich W., Rudel T., Heesemann J., Goebel W. (2020). Persistence of Intracellular Bacterial Pathogens-With a Focus on the Metabolic Perspective. Front. Cell Infect. Microbiol. 10, 615450. doi: 10.3389/fcimb.2020.615450
    1. Esterhazy D., King M. S., Yakovlev G., Hirst J. (2008). Production of Reactive Oxygen Species by Complex I (NADH:ubiquinone Oxidoreductase) From Escherichia Coli and Comparison to the Enzyme From Mitochondria. Biochemistry 47, 3964–3971. doi: 10.1021/bi702243b
    1. Falkinham J. O., Wall T. E., 3rd, Tanner J. R., Tawaha K., Alali F. Q., Li C., et al. . (2009). Proliferation of Antibiotic-Producing Bacteria and Concomitant Antibiotic Production as the Basis for the Antibiotic Activity of Jordan's Red Soils. Appl. Environ. Microbiol. 75, 2735–2741. doi: 10.1128/AEM.00104-09
    1. Fauvart M., De Groote V. N., Michiels J. (2011). Role of Persister Cells in Chronic Infections: Clinical Relevance and Perspectives on Anti-Persister Therapies. J. Med. Microbiol. 60, 699–709. doi: 10.1099/jmm.0.030932-0
    1. Fisher R. A., Gollan B., Helaine S. (2017). Persistent Bacterial Infections and Persister Cells. Nat. Rev. Microbiol. 15, 453–464. doi: 10.1038/nrmicro.2017.42
    1. Fisher J. F., Mobashery S. (2020). Constructing and Deconstructing the Bacterial Cell Wall. Protein Sci. 29, 629–646. doi: 10.1002/pro.3737
    1. Fluit A. C., Schmitz F. J. (2004). Resistance Integrons and Super-Integrons. Clin. Microbiol. Infect. 10, 272–288. doi: 10.1111/j.1198-743X.2004.00858.x
    1. Foster P. L. (2007). Stress-Induced Mutagenesis in Bacteria. Crit. Rev. Biochem. Mol. Biol. 42, 373–397. doi: 10.1080/10409230701648494
    1. Foster J. W., Woodruff H. B. (2010). Antibiotic Substances Produced by Bacteria. Ann. N Y Acad. Sci. 1213, 125–136. doi: 10.1111/j.1749-6632.2010.05887.x
    1. Fowler R. G., Schaaper R. M. (1997). The Role of the mutT Gene of Escherichia Coli in Maintaining Replication Fidelity. FEMS Microbiol. Rev. 21, 43–54. doi: 10.1111/j.1574-6976.1997.tb00344.x
    1. Friedberg E. C., Aguilera A., Gellert M., Hanawalt P. C., Hays J. B., Lehmann A. R., et al. . (2006. b). DNA Repair: From Molecular Mechanism to Human Disease. DNA Repair (Amst). 5, 986–996. doi: 10.1016/j.dnarep.2006.05.005
    1. Friedberg C. E., Walker C. G., Siede W., Wood D. R., Schultz A. R., Ellenberger T. (2006. a). DNA Repair and Mutagenesis, Second Edition (Washington DC: American Society of Microbiology; ).
    1. Fuchs R. P., Fujii S. (2013). Translesion DNA Synthesis and Mutagenesis in Prokaryotes. Cold Spring Harb. Perspect. Biol. 5, a012682. doi: 10.1101/cshperspect.a012682
    1. Fujii S., Fuchs R. P. (2020). A Comprehensive View of Translesion Synthesis in Escherichia Coli . Microbiol. Mol. Biol. Rev. 84. doi: 10.1128/MMBR.00002-20
    1. Fung D. K., Chan E. W., Chin M. L., Chan R. C. (2010). Delineation of a Bacterial Starvation Stress Response Network Which can Mediate Antibiotic Tolerance Development. Antimicrob. Agents Chemother. 54, 1082–1093. doi: 10.1128/AAC.01218-09
    1. Gagneux S., Small P. M. (2007). Global Phylogeography of Mycobacterium Tuberculosis and Implications for Tuberculosis Product Development. Lancet Infect. Dis. 7, 328–337. doi: 10.1016/S1473-3099(07)70108-1
    1. George A. M. (1996). Multidrug Resistance in Enteric and Other Gram-Negative Bacteria. FEMS Microbiol. Lett. 139, 1–10. doi: 10.1111/j.1574-6968.1996.tb08172.x
    1. Gerdes K. (2016). Hypothesis: Type I Toxin-Antitoxin Genes Enter the Persistence Field-a Feedback Mechanism Explaining Membrane Homoeostasis. Philos. Trans. R Soc. Lond. B Biol. Sci. 371. doi: 10.1098/rstb.2016.0189
    1. Germain E., Roghanian M., Gerdes K., Maisonneuve E. (2015). Stochastic Induction of Persister Cells by HipA Through (P)Ppgpp-Mediated Activation of mRNA Endonucleases. Proc. Natl. Acad. Sci. U.S.A. 112, 5171–5176. doi: 10.1073/pnas.1423536112
    1. Girard P. M., Boiteux S. (1997). Repair of Oxidized DNA Bases in the Yeast Saccharomyces Cerevisiae . Biochimie 79, 559–566. doi: 10.1016/S0300-9084(97)82004-4
    1. Glen K. A., Lamont I. L. (2021). Beta-Lactam Resistance in Pseudomonas Aeruginosa: Current Status, Future Prospects. Pathogens 10. doi: 10.3390/pathogens10121638
    1. Gollan B., Grabe G., Michaux C., Helaine S. (2019). Bacterial Persisters and Infection: Past, Present, and Progressing. Annu. Rev. Microbiol. 73, 359–385. doi: 10.1146/annurev-micro-020518-115650
    1. Golub E., Bailone A., Devoret R. (1988). A Gene Encoding an SOS Inhibitor is Present in Different Conjugative Plasmids. J. Bacteriol. 170, 4392–4394. doi: 10.1128/jb.170.9.4392-4394.1988
    1. Gomes C., Martinez-Puchol S., Ruiz-Roldan L., Pons M. J., Del Valle Mendoza J., Ruiz J. (2016). Development and Characterisation of Highly Antibiotic Resistant Bartonella Bacilliformis Mutants. Sci. Rep. 6, 33584. doi: 10.1038/srep33584
    1. Goodman M. F., Woodgate R. (2013). Translesion DNA Polymerases. Cold Spring Harb. Perspect. Biol. 5, a010363. doi: 10.1101/cshperspect.a010363
    1. Grant S. S., Hung D. T. (2013). Persistent Bacterial Infections, Antibiotic Tolerance, and the Oxidative Stress Response. Virulence 4, 273–283. doi: 10.4161/viru.23987
    1. Grant S. S., Kaufmann B. B., Chand N. S., Haseley N., Hung D. T. (2012). Eradication of Bacterial Persisters With Antibiotic-Generated Hydroxyl Radicals. Proc. Natl. Acad. Sci. U.S.A. 109, 12147–12152. doi: 10.1073/pnas.1203735109
    1. Grimwade J. E., Leonard A. C. (2019). Blocking the Trigger: Inhibition of the Initiation of Bacterial Chromosome Replication as an Antimicrobial Strategy. Antibiot. (Basel) 8. doi: 10.3390/antibiotics8030111
    1. Gross M. H., Konieczny I. (2020). Polyphosphate Induces the Proteolysis of ADP-Bound Fraction of Initiator to Inhibit DNA Replication Initiation Upon Stress in Escherichia Coli . Nucleic Acids Res. 48, 5457–5466. doi: 10.1093/nar/gkaa217
    1. Grubmüller S., Schauer K., Goebel W., Fuchs T. M., Eisenreich W. (2014). Analysis of Carbon Substrates Used by Listeria Monocytogenes During Growth in J774A.1 Macrophages Suggests a Bipartite Intracellular Metabolism. Front. Cell Infect. Microbiol. 4, 156. doi: 10.3389/fcimb.2014.00156
    1. Gutierrez A., Jain S., Bhargava P., Hamblin M., Lobritz M. A., Collins J. J. (2017). Understanding and Sensitizing Density-Dependent Persistence to Quinolone Antibiotics. Mol. Cell 68, 1147–1154 e1143. doi: 10.1016/j.molcel.2017.11.012
    1. Gygli S. M., Borrell S., Trauner A., Gagneux S. (2017). Antimicrobial Resistance in Mycobacterium Tuberculosis: Mechanistic and Evolutionary Perspectives. FEMS Microbiol. Rev. 41, 354–373. doi: 10.1093/femsre/fux011
    1. Hackstadt T., Williams J. C. (1981). Biochemical Stratagem for Obligate Parasitism of Eukaryotic Cells by Coxiella Burnetii . Proc. Natl. Acad. Sci. U.S.A. 78, 3240–3244. doi: 10.1073/pnas.78.5.3240
    1. Halden R. U., Paull D. H. (2005). Co-Occurrence of Triclocarban and Triclosan in U.S. Water Resources. Environ. Sci. Technol. 39, 1420–1426. doi: 10.1021/es049071e
    1. Handel N., Hoeksema M., Freijo Mata M., Brul S., Ter Kuile B. H. (2015). Effects of Stress, Reactive Oxygen Species, and the SOS Response on De Novo Acquisition of Antibiotic Resistance in Escherichia Coli . Antimicrob. Agents Chemother. 60, 1319–1327. doi: 10.1128/AAC.02684-15
    1. Hansen F. G., Atlung T. (2018). The DnaA Tale. Front. Microbiol. 9, 319. doi: 10.3389/fmicb.2018.00319
    1. Harms A., Maisonneuve E., Gerdes K. (2016). Mechanisms of Bacterial Persistence During Stress and Antibiotic Exposure. Science 354. doi: 10.1126/science.aaf4268
    1. Hartman T. E., Wang Z., Jansen R. S., Gardete S., Rhee K. Y. (2017). Metabolic Perspectives on Persistence. Microbiol. Spectr. 5. doi: 10.1128/9781555819569.ch31
    1. Hastings P. J., Rosenberg S. M., Slack A. (2004). Antibiotic-Induced Lateral Transfer of Antibiotic Resistance. Trends Microbiol. 12, 401–404. doi: 10.1016/j.tim.2004.07.003
    1. Headd B., Bradford S. A. (2018). Physicochemical Factors That Favor Conjugation of an Antibiotic Resistant Plasmid in non-Growing Bacterial Cultures in the Absence and Presence of Antibiotics. Front. Microbiol. 9, 2122. doi: 10.3389/fmicb.2018.02122
    1. Hebrard M., Viala J. P., Meresse S., Barras F., Aussel L. (2009). Redundant Hydrogen Peroxide Scavengers Contribute to Salmonella Virulence and Oxidative Stress Resistance. J. Bacteriol. 191, 4605–4614. doi: 10.1128/JB.00144-09
    1. Heide L. (2014). New Aminocoumarin Antibiotics as Gyrase Inhibitors. Int. J. Med. Microbiol. 304, 31–36. doi: 10.1016/j.ijmm.2013.08.013
    1. Heisig P. (2009). Type II Topoisomerases–Inhibitors, Repair Mechanisms and Mutations. Mutagenesis 24, 465–469. doi: 10.1093/mutage/gep035
    1. Henle E. S., Linn S. (1997). Formation, Prevention, and Repair of DNA Damage by Iron/Hydrogen Peroxide. J. Biol. Chem. 272, 19095–19098. doi: 10.1074/jbc.272.31.19095
    1. Henrikus S. S., Van Oijen A. M., Robinson A. (2018). Specialised DNA Polymerases in Escherichia Coli: Roles Within Multiple Pathways. Curr. Genet. 64, 1189–1196. doi: 10.1007/s00294-018-0840-x
    1. Hogardt M., Hoboth C., Schmoldt S., Henke C., Bader L., Heesemann J. (2007). Stage-Specific Adaptation of Hypermutable Pseudomonas Aeruginosa Isolates During Chronic Pulmonary Infection in Patients With Cystic Fibrosis. J. Infect. Dis. 195, 70–80. doi: 10.1086/509821
    1. Hong Y., Zeng J., Wang X., Drlica K., Zhao X. (2019). Post-Stress Bacterial Cell Death Mediated by Reactive Oxygen Species. Proc. Natl. Acad. Sci. U.S.A. 116, 10064–10071. doi: 10.1073/pnas.1901730116
    1. Hooper D. C. (2001). Mechanisms of Action of Antimicrobials: Focus on Fluoroquinolones. Clin. Infect. Dis. 32 Suppl 1, S9–S15. doi: 10.1086/319370
    1. Hooper D. C., Jacoby G. A. (2015). Mechanisms of Drug Resistance: Quinolone Resistance. Ann. N Y Acad. Sci. 1354, 12–31. doi: 10.1111/nyas.12830
    1. Hooper D. C., Jacoby G. A. (2016). Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance. Cold Spring Harb. Perspect. Med. 6. doi: 10.1101/cshperspect.a025320
    1. Huemer M., Mairpady Shambat S., Brugger S. D., Zinkernagel A. S. (2020). Antibiotic Resistance and Persistence-Implications for Human Health and Treatment Perspectives. EMBO Rep. 21, e51034. doi: 10.15252/embr.202051034
    1. Imlay J. A. (2003). Pathways of Oxidative Damage. Annu. Rev. Microbiol. 57, 395–418. doi: 10.1146/annurev.micro.57.030502.090938
    1. Imlay J. A. (2006). Iron-Sulphur Clusters and the Problem With Oxygen. Mol. Microbiol. 59, 1073–1082. doi: 10.1111/j.1365-2958.2006.05028.x
    1. Imlay J. A., Linn S. (1987). Mutagenesis and Stress Responses Induced in Escherichia Coli by Hydrogen Peroxide. J. Bacteriol. 169, 2967–2976. doi: 10.1128/jb.169.7.2967-2976.1987
    1. Johnston C., Martin B., Fichant G., Polard P., Claverys J. P. (2014). Bacterial Transformation: Distribution, Shared Mechanisms and Divergent Control. Nat. Rev. Microbiol. 12, 181–196. doi: 10.1038/nrmicro3199
    1. Jolivet-Gougeon A., Kovacs B., Le Gall-David S., Le Bars H., Bousarghin L., Bonnaure-Mallet M., et al. . (2011). Bacterial Hypermutation: Clinical Implications. J. Med. Microbiol. 60, 563–573. doi: 10.1099/jmm.0.024083-0
    1. Jones M. E., Peters E., Weersink A. M., Fluit A., Verhoef J. (1997). Widespread Occurrence of Integrons Causing Multiple Antibiotic Resistance in Bacteria. Lancet 349, 1742–1743. doi: 10.1016/S0140-6736(05)62954-6
    1. Joseph A. M., Badrinarayanan A. (2020). Visualizing Mutagenic Repair: Novel Insights Into Bacterial Translesion Synthesis. FEMS Microbiol. Rev. 44, 572–582. doi: 10.1093/femsre/fuaa023
    1. Jung S. H., Ryu C. M., Kim J. S. (2019). Bacterial Persistence: Fundamentals and Clinical Importance. J. Microbiol. 57, 829–835. doi: 10.1007/s12275-019-9218-0
    1. Kaguni J. M. (2006). DnaA: Controlling the Initiation of Bacterial DNA Replication and More. Annu. Rev. Microbiol. 60, 351–375. doi: 10.1146/annurev.micro.60.080805.142111
    1. Katayama T., Kasho K., Kawakami H. (2017). The DnaA Cycle in Escherichia Coli: Activation, Function and Inactivation of the Initiator Protein. Front. Microbiol. 8, 2496. doi: 10.3389/fmicb.2017.02496
    1. Kaushik M., Kumar S., Kapoor R. K., Gulati P. (2019). Integrons and Antibiotic Resistance Genes in Water-Borne Pathogens: Threat Detection and Risk Assessment. J. Med. Microbiol. 68, 679–692. doi: 10.1099/jmm.0.000972
    1. Kawai Y., Mercier R., Wu L. J., Dominguez-Cuevas P., Oshima T., Errington J. (2015). Cell Growth of Wall-Free L-Form Bacteria is Limited by Oxidative Damage. Curr. Biol. 25, 1613–1618. doi: 10.1016/j.cub.2015.04.031
    1. Kazar J. (2005). Coxiella Burnetii Infection. Ann. N Y Acad. Sci. 1063, 105–114. doi: 10.1196/annals.1355.018
    1. Kedzierska B., Hayes F. (2016). Emerging Roles of Toxin-Antitoxin Modules in Bacterial Pathogenesis. Molecules 21. doi: 10.3390/molecules21060790
    1. Keren I., Mulcahy L. R., Lewis K. (2012). Persister Eradication: Lessons From the World of Natural Products. Methods Enzymol. 517, 387–406. doi: 10.1016/B978-0-12-404634-4.00019-X
    1. Keren I., Wu Y., Inocencio J., Mulcahy L. R., Lewis K. (2013). Killing by Bactericidal Antibiotics Does Not Depend on Reactive Oxygen Species. Science 339, 1213–1216. doi: 10.1126/science.1232688
    1. Ketkar A., Maddukuri L., Penthala N. R., Reed M. R., Zafar M. K., Crooks P. A., et al. . (2019). Inhibition of Human DNA Polymerases Eta and Kappa by Indole-Derived Molecules Occurs Through Distinct Mechanisms. ACS Chem. Biol. 14, 1337–1351. doi: 10.1021/acschembio.9b00304
    1. Kim J. S., Cho D. H., Heo P., Jung S. C., Park M., Oh E. J., et al. . (2016). Fumarate-Mediated Persistence of Escherichia Coli Against Antibiotics. Antimicrob. Agents Chemother. 60, 2232–2240. doi: 10.1128/AAC.01794-15
    1. Kim J. S., Heo P., Yang T. J., Lee K. S., Cho D. H., Kim B. T., et al. . (2011). Selective Killing of Bacterial Persisters by a Single Chemical Compound Without Affecting Normal Antibiotic-Sensitive Cells. Antimicrob. Agents Chemother. 55, 5380–5383. doi: 10.1128/AAC.00708-11
    1. Kohanski M. A., Dwyer D. J., Collins J. J. (2010). How Antibiotics Kill Bacteria: From Targets to Networks. Nat. Rev. Microbiol. 8, 423–435. doi: 10.1038/nrmicro2333
    1. Kohanski M. A., Dwyer D. J., Hayete B., Lawrence C. A., Collins J. J. (2007). A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics. Cell 130, 797–810. doi: 10.1016/j.cell.2007.06.049
    1. Kohanski M. A., Dwyer D. J., Wierzbowski J., Cottarel G., Collins J. J. (2008). Mistranslation of Membrane Proteins and Two-Component System Activation Trigger Antibiotic-Mediated Cell Death. Cell 135, 679–690. doi: 10.1016/j.cell.2008.09.038
    1. Korch S. B., Henderson T. A., Hill T. M. (2003). Characterization of the Hipa7 Allele of Escherichia Coli and Evidence That High Persistence is Governed by (P)Ppgpp Synthesis. Mol. Microbiol. 50, 1199–1213. doi: 10.1046/j.1365-2958.2003.03779.x
    1. Korshunov S., Imlay J. A. (2010). Two Sources of Endogenous Hydrogen Peroxide in Escherichia Coli . Mol. Microbiol. 75, 1389–1401. doi: 10.1111/j.1365-2958.2010.07059.x
    1. Kraemer J. A., Sanderlin A. G., Laub M. T. (2019). The Stringent Response Inhibits DNA Replication Initiation in E. Coli by Modulating Supercoiling of oriC . mBio 10. doi: 10.1128/mBio.01330-19
    1. Krause K. M., Serio A. W., Kane T. R., Connolly L. E. (2016). Aminoglycosides: An Overview. Cold Spring Harb. Perspect. Med. 6. doi: 10.1101/cshperspect.a027029
    1. Kreuzer K. N. (2013). DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks. Cold Spring Harb. Perspect. Biol. 5, a012674. doi: 10.1101/cshperspect.a012674
    1. Kuang D., Zhang J., Xu X., Shi W., Chen S., Yang X., et al. . (2018). Emerging High-Level Ciprofloxacin Resistance and Molecular Basis of Resistance in Salmonella Enterica From Humans, Food and Animals. Int. J. Food Microbiol. 280, 1–9. doi: 10.1016/j.ijfoodmicro.2018.05.001
    1. Kwan B. W., Valenta J. A., Benedik M. J., Wood T. K. (2013). Arrested Protein Synthesis Increases Persister-Like Cell Formation. Antimicrob. Agents Chemother. 57, 1468–1473. doi: 10.1128/AAC.02135-12
    1. Larsson D. G. J., Flach C. F. (2022). Antibiotic Resistance in the Environment. Nat. Rev. Microbiol. 20, 257–269. doi: 10.1038/s41579-021-00649-x
    1. Lawrence J. G. (1999). Gene Transfer, Speciation, and the Evolution of Bacterial Genomes. Curr. Opin. Microbiol. 2, 519–523. doi: 10.1016/S1369-5274(99)00010-7
    1. Lee C. A., Grossman A. D. (2007). Identification of the Origin of Transfer (Orit) and DNA Relaxase Required for Conjugation of the Integrative and Conjugative Element ICEBs1 of Bacillus Subtilis . J. Bacteriol. 189, 7254–7261. doi: 10.1128/JB.00932-07
    1. Leger L., Budin-Verneuil A., Cacaci M., Benachour A., Hartke A., Verneuil N. (2019). Beta-Lactam Exposure Triggers Reactive Oxygen Species Formation in Enterococcus Faecalis via the Respiratory Chain Component DMK. Cell Rep. 29, 2184–2191 e2183. doi: 10.1016/j.celrep.2019.10.080
    1. Leonard A. C., Grimwade J. E. (2010). Regulating DnaA Complex Assembly: It is Time to Fill the Gaps. Curr. Opin. Microbiol. 13, 766–772. doi: 10.1016/j.mib.2010.10.001
    1. Leonard A. C., Grimwade J. E. (2015). The Orisome: Structure and Function. Front. Microbiol. 6, 545. doi: 10.3389/fmicb.2015.00545
    1. Leonard A. C., Rao P., Kadam R. P., Grimwade J. E. (2019). Changing Perspectives on the Role of DnaA-ATP in Orisome Function and Timing Regulation. Front. Microbiol. 10, 2009. doi: 10.3389/fmicb.2019.02009
    1. Levin-Reisman I., Brauner A., Ronin I., Balaban N. Q. (2019). Epistasis Between Antibiotic Tolerance, Persistence, and Resistance Mutations. Proc. Natl. Acad. Sci. U.S.A. 116, 14734–14739. doi: 10.1073/pnas.1906169116
    1. Lewis K. (2007). Persister Cells, Dormancy and Infectious Disease. Nat. Rev. Microbiol. 5, 48–56. doi: 10.1038/nrmicro1557
    1. Li B., Qiu Y., Song Y., Lin H., Yin H. (2019. a). Dissecting Horizontal and Vertical Gene Transfer of Antibiotic Resistance Plasmid in Bacterial Community Using Microfluidics. Environ. Int. 131, 105007. doi: 10.1016/j.envint.2019.105007
    1. Lister P. D., Wolter D. J., Hanson N. D. (2009). Antibacterial-Resistant Pseudomonas Aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms. Clin. Microbiol. Rev. 22, 582–610. doi: 10.1128/CMR.00040-09
    1. Little J. W., Mount D. W. (1982). The SOS Regulatory System of Escherichia Coli . Cell 29, 11–22. doi: 10.1016/0092-8674(82)90085-X
    1. Liu G., Bogaj K., Bortolaia V., Olsen J. E., Thomsen L. E. (2019). Antibiotic-Induced, Increased Conjugative Transfer is Common to Diverse Naturally Occurring ESBL Plasmids in Escherichia Coli . Front. Microbiol. 10, 2119. doi: 10.3389/fmicb.2019.02119
    1. Liu Y., Imlay J. A. (2013). Cell Death From Antibiotics Without the Involvement of Reactive Oxygen Species. Science 339, 1210–1213. doi: 10.1126/science.1232751
    1. Liu P., Wu Z., Xue H., Zhao X. (2017. a). Antibiotics Trigger Initiation of SCCmec Transfer by Inducing SOS Responses. Nucleic Acids Res. 45, 3944–3952. doi: 10.1093/nar/gkx153
    1. Liu S., Wu N., Zhang S., Yuan Y., Zhang W., Zhang Y. (2017. b). Variable Persister Gene Interactions With (P)Ppgpp for Persister Formation in Escherichia Coli . Front. Microbiol. 8, 1795. doi: 10.3389/fmicb.2017.01795
    1. Li X., Zhang Y., Zhou X., Hu X., Zhou Y., Liu D., et al. . (2019. b). The Plasmid-Borne Quinolone Resistance Protein QnrB, a Novel DnaA-Binding Protein, Increases the Bacterial Mutation Rate by Triggering DNA Replication Stress. Mol. Microbiol. 111, 1529–1543. doi: 10.1111/mmi.14235
    1. Li Y., Zhang L., Zhou Y., Zhang Z., Zhang X. (2018). Survival of Bactericidal Antibiotic Treatment by Tolerant Persister Cells of Klebsiella Pneumoniae . J. Med. Microbiol. 67, 273–281. doi: 10.1099/jmm.0.000680
    1. Lopatkin A. J., Huang S., Smith R. P., Srimani J. K., Sysoeva T. A., Bewick S., et al. . (2016). Antibiotics as a Selective Driver for Conjugation Dynamics. Nat. Microbiol. 1, 16044. doi: 10.1038/nmicrobiol.2016.44
    1. Lopez-Causape C., Cabot G., Del Barrio-Tofino E., Oliver A. (2018). The Versatile Mutational Resistome of Pseudomonas Aeruginosa . Front. Microbiol. 9, 685. doi: 10.3389/fmicb.2018.00685
    1. López E., Elez M., Matic I., Blázquez J. (2007). Antibiotic-Mediated Recombination: Ciprofloxacin Stimulates SOS-Independent Recombination of Divergent Sequences in Escherichia Coli . Mol. Microbiol. 64, 83–93. doi: 10.1111/j.1365-2958.2007.05642.x
    1. Lu J., Wang Y., Li J., Mao L., Nguyen S. H., Duarte T., et al. . (2018). Triclosan at Environmentally Relevant Concentrations Promotes Horizontal Transfer of Multidrug Resistance Genes Within and Across Bacterial Genera. Environ. Int. 121, 1217–1226. doi: 10.1016/j.envint.2018.10.040
    1. MacPhee D. G., Ambrose M. (2010). Catabolite Repression of SOS-Dependent and SOS-Independent Spontaneous Mutagenesis in Stationary-Phase Escherichia Coli . Mutat. Res. 686, 84–89. doi: 10.1016/j.mrfmmm.2010.01.022
    1. Magnet S., Blanchard J. S. (2005). Molecular Insights Into Aminoglycoside Action and Resistance. Chem. Rev. 105, 477–498. doi: 10.1021/cr0301088
    1. Maiques E., Ubeda C., Campoy S., Salvador N., Lasa I., Novick R. P., et al. . (2006). Beta-Lactam Antibiotics Induce the SOS Response and Horizontal Transfer of Virulence Factors in Staphylococcus Aureus . J. Bacteriol. 188, 2726–2729. doi: 10.1128/JB.188.7.2726-2729.2006
    1. Maisonneuve E., Gerdes K. (2014). Molecular Mechanisms Underlying Bacterial Persisters. Cell 157, 539–548. doi: 10.1016/j.cell.2014.02.050
    1. Maisonneuve E., Shakespeare L. J., Jorgensen M. G., Gerdes K. (2011). Bacterial Persistence by RNA Endonucleases. Proc. Natl. Acad. Sci. U.S.A. 108, 13206–13211. doi: 10.1073/pnas.1100186108
    1. Makise M., Mima S., Katsu T., Tsuchiya T., Mizushima T. (2002). Acidic Phospholipids Inhibit the DNA-Binding Activity of DnaA Protein, the Initiator of Chromosomal DNA Replication in Escherichia Coli . Mol. Microbiol. 46, 245–256. doi: 10.1046/j.1365-2958.2002.03161.x
    1. Manson J. M., Hancock L. E., Gilmore M. S. (2010). Mechanism of Chromosomal Transfer of Enterococcus Faecalis Pathogenicity Island, Capsule, Antimicrobial Resistance, and Other Traits. Proc. Natl. Acad. Sci. U.S.A. 107, 12269–12274. doi: 10.1073/pnas.1000139107
    1. Maor-Shoshani A., Reuven N. B., Tomer G., Livneh Z. (2000). Highly Mutagenic Replication by DNA Polymerase V (UmuC) Provides a Mechanistic Basis for SOS Untargeted Mutagenesis. Proc. Natl. Acad. Sci. U.S.A. 97, 565–570. doi: 10.1073/pnas.97.2.565
    1. Marians K. J. (2018). Lesion Bypass and the Reactivation of Stalled Replication Forks. Annu. Rev. Biochem. 87, 217–238. doi: 10.1146/annurev-biochem-062917-011921
    1. Marnef A., Cohen S., Legube G. (2017). Transcription-Coupled DNA Double-Strand Break Repair: Active Genes Need Special Care. J. Mol. Biol. 429, 1277–1288. doi: 10.1016/j.jmb.2017.03.024
    1. Martinez J. L. (2008). Antibiotics and Antibiotic Resistance Genes in Natural Environments. Science 321, 365–367. doi: 10.1126/science.1159483
    1. Martinez J. L. (2014). General Principles of Antibiotic Resistance in Bacteria. Drug Discovery Today Technol. 11, 33–39. doi: 10.1016/j.ddtec.2014.02.001
    1. Martinez J. L., Baquero F. (2000). Mutation Frequencies and Antibiotic Resistance. Antimicrob. Agents Chemother. 44, 1771–1777. doi: 10.1128/AAC.44.7.1771-1777.2000
    1. Martinez J. L., Baquero F. (2002). Interactions Among Strategies Associated With Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance. Clin. Microbiol. Rev. 15, 647–679. doi: 10.1128/CMR.15.4.647-679.2002
    1. Martin B., Garcia P., Castanie M. P., Claverys J. P. (1995). The recA Gene of Streptococcus Pneumoniae is Part of a Competence-Induced Operon and Controls Lysogenic Induction. Mol. Microbiol. 15, 367–379. doi: 10.1111/j.1365-2958.1995.tb02250.x
    1. Maslowska K. H., Makiela-Dzbenska K., Fijalkowska I. J. (2019). The SOS System: A Complex and Tightly Regulated Response to DNA Damage. Environ. Mol. Mutagen. 60, 368–384. doi: 10.1002/em.22267
    1. Matsunaga K., Yamaki H., Nishimura T., Tanaka N. (1986). Inhibition of DNA Replication Initiation by Aminoglycoside Antibiotics. Antimicrob. Agents Chemother. 30, 468–474. doi: 10.1128/AAC.30.3.468
    1. Maurin M., Raoult D. (1999). Q Fever. Clin. Microbiol. Rev. 12, 518–553. doi: 10.1128/CMR.12.4.518
    1. McBee M. E., Chionh Y. H., Sharaf M. L., Ho P., Cai M. W., Dedon P. C. (2017). Production of Superoxide in Bacteria is Stress- and Cell State-Dependent: A Gating-Optimized Flow Cytometry Method That Minimizes ROS Measurement Artifacts With Fluorescent Dyes. Front. Microbiol. 8, 459. doi: 10.3389/fmicb.2017.00459
    1. McMillan E. A., Jackson C. R., Frye J. G. (2020). Transferable Plasmids of Salmonella Enterica Associated With Antibiotic Resistance Genes. Front. Microbiol. 11, 562181. doi: 10.3389/fmicb.2020.562181
    1. Mertens K., Lantsheer L., Ennis D. G., Samuel J. E. (2008). Constitutive SOS Expression and Damage-Inducible AddAB-Mediated Recombinational Repair Systems for Coxiella Burnetii as Potential Adaptations for Survival Within Macrophages. Mol. Microbiol. 69, 1411–1426. doi: 10.1111/j.1365-2958.2008.06373.x
    1. Messner K. R., Imlay J. A. (2002). Mechanism of Superoxide and Hydrogen Peroxide Formation by Fumarate Reductase, Succinate Dehydrogenase, and Aspartate Oxidase. J. Biol. Chem. 277, 42563–42571. doi: 10.1074/jbc.M204958200
    1. Mestrovic T., Ljubin-Sternak S. (2018). Molecular Mechanisms of Chlamydia Trachomatis Resistance to Antimicrobial Drugs. Front. Biosci. (Landmark Ed) 23, 656–670. doi: 10.2741/4611
    1. Meylan S., Porter C. B. M., Yang J. H., Belenky P., Gutierrez A., Lobritz M. A., et al. . (2017). Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas Aeruginosa via Tricarboxylic Acid Cycle Control. Cell Chem. Biol. 24, 195–206. doi: 10.1016/j.chembiol.2016.12.015
    1. Miller C., Thomsen L. E., Gaggero C., Mosseri R., Ingmer H., Cohen S. N. (2004). SOS Response Induction by Beta-Lactams and Bacterial Defense Against Antibiotic Lethality. Science 305, 1629–1631. doi: 10.1126/science.1101630
    1. Minarini L. A., Darini A. L. (2012). Mutations in the Quinolone Resistance-Determining Regions of gyrA and parC in Enterobacteriaceae Isolates From Brazil. Braz. J. Microbiol. 43, 1309–1314. doi: 10.1590/S1517-83822012000400010
    1. Mizuuchi K., Fisher L. M., O'dea M. H., Gellert M. (1980). DNA Gyrase Action Involves the Introduction of Transient Double-Strand Breaks Into DNA. Proc. Natl. Acad. Sci. U.S.A. 77, 1847–1851. doi: 10.1073/pnas.77.4.1847
    1. Modell J. W., Kambara T. K., Perchuk B. S., Laub M. T. (2014). A DNA Damage-Induced, SOS-Independent Checkpoint Regulates Cell Division in Caulobacter Crescentus . PloS Biol. 12, e1001977. doi: 10.1371/journal.pbio.1001977
    1. Mok W. W. K., Brynildsen M. P. (2018). Timing of DNA Damage Responses Impacts Persistence to Fluoroquinolones. Proc. Natl. Acad. Sci. U.S.A. 115, E6301–E6309. doi: 10.1073/pnas.1804218115
    1. Mok W. W., Orman M. A., Brynildsen M. P. (2015). Impacts of Global Transcriptional Regulators on Persister Metabolism. Antimicrob. Agents Chemother. 59, 2713–2719. doi: 10.1128/AAC.04908-14
    1. Moldoveanu A. L., Rycroft J. A., Helaine S. (2021). Impact of Bacterial Persisters on Their Host. Curr. Opin. Microbiol. 59, 65–71. doi: 10.1016/j.mib.2020.07.006
    1. Mo C. Y., Manning S. A., Roggiani M., Culyba M. J., Samuels A. N., Sniegowski P. D., et al. . (2016). Systematically Altering Bacterial SOS Activity Under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics. mSphere 1. doi: 10.1128/mSphere.00163-16
    1. Mulcahy L. R., Burns J. L., Lory S., Lewis K. (2010). Emergence of Pseudomonas Aeruginosa Strains Producing High Levels of Persister Cells in Patients With Cystic Fibrosis. J. Bacteriol. 192, 6191–6199. doi: 10.1128/JB.01651-09
    1. Mundt J. M., Hah S. S., Sumbad R. A., Schramm V., Henderson P. T. (2008). Incorporation of Extracellular 8-oxodG Into DNA and RNA Requires Purine Nucleoside Phosphorylase in MCF-7 Cells. Nucleic Acids Res. 36, 228–236. doi: 10.1093/nar/gkm1032
    1. Munita J. M., Arias C. A. (2016). Mechanisms of Antibiotic Resistance. Microbiol. Spectr. 4. doi: 10.1128/9781555819286.ch17
    1. Neher S. B., Flynn J. M., Sauer R. T., Baker T. A. (2003). Latent ClpX-Recognition Signals Ensure LexA Destruction After DNA Damage. Genes Dev. 17, 1084–1089. doi: 10.1101/gad.1078003
    1. Neil K., Allard N., Rodrigue S. (2021). Molecular Mechanisms Influencing Bacterial Conjugation in the Intestinal Microbiota. Front. Microbiol. 12, 673260. doi: 10.3389/fmicb.2021.673260
    1. Nicoloff H., Hjort K., Levin B. R., Andersson D. I. (2019). The High Prevalence of Antibiotic Heteroresistance in Pathogenic Bacteria is Mainly Caused by Gene Amplification. Nat. Microbiol. 4, 504–514. doi: 10.1038/s41564-018-0342-0
    1. Nikaido H. (1985). Role of Permeability Barriers in Resistance to Beta-Lactam Antibiotics. Pharmacol. Ther. 27, 197–231. doi: 10.1016/0163-7258(85)90069-5
    1. Nitiss K. C., Nitiss J. L., Hanakahi L. A. (2019). DNA Damage by an Essential Enzyme: A Delicate Balance Act on the Tightrope. DNA Repair (Amst). 82, 102639. doi: 10.1016/j.dnarep.2019.102639
    1. Norton M. D., Spilkia A. J., Godoy V. G. (2013). Antibiotic Resistance Acquired Through a DNA Damage-Inducible Response in Acinetobacter Baumannii . J. Bacteriol. 195, 1335–1345. doi: 10.1128/JB.02176-12
    1. Olaimat A. N., Al-Holy M. A., Shahbaz H. M., Al-Nabulsi A. A., Abu Ghoush M. H., Osaili T. M., et al. . (2018). Emergence of Antibiotic Resistance in Listeria Monocytogenes Isolated From Food Products: A Comprehensive Review. Compr. Rev. Food Sci. Food Saf. 17, 1277–1292. doi: 10.1111/1541-4337.12387
    1. Oliver A., Mena A. (2010). Bacterial Hypermutation in Cystic Fibrosis, Not Only for Antibiotic Resistance. Clin. Microbiol. Infect. 16, 798–808. doi: 10.1111/j.1469-0691.2010.03250.x
    1. Orman M. A., Brynildsen M. P. (2013). Dormancy is Not Necessary or Sufficient for Bacterial Persistence. Antimicrob. Agents Chemother. 57, 3230–3239. doi: 10.1128/AAC.00243-13
    1. Orman M. A., Mok W. W., Brynildsen M. P. (2015). Aminoglycoside-Enabled Elucidation of Bacterial Persister Metabolism. Curr. Protoc. Microbiol. 36 17, 19 11–19 14. doi: 10.1002/9780471729259.mc1709s36
    1. Pages V., Fuchs R. P. (2002). How DNA Lesions are Turned Into Mutations Within Cells? Oncogene 21, 8957–8966. doi: 10.1038/sj.onc.1206006
    1. Palmen R., Driessen A. J., Hellingwerf K. J. (1994). Bioenergetic Aspects of the Translocation of Macromolecules Across Bacterial Membranes. Biochim. Biophys. Acta 1183, 417–451. doi: 10.1016/0005-2728(94)90072-8
    1. Panzetta M. E., Valdivia R. H., Saka H. A. (2018). Chlamydia Persistence: A Survival Strategy to Evade Antimicrobial Effects in-Vitro and in-Vivo . Front. Microbiol. 9, 3101. doi: 10.3389/fmicb.2018.03101
    1. Partridge S. R., Kwong S. M., Firth N., Jensen S. O. (2018). Mobile Genetic Elements Associated With Antimicrobial Resistance. Clin. Microbiol. Rev. 31. doi: 10.1128/CMR.00088-17
    1. Patel A., Malinovska L., Saha S., Wang J., Alberti S., Krishnan Y., et al. . (2017). ATP as a Biological Hydrotrope. Science 356, 753–756. doi: 10.1126/science.aaf6846
    1. Peacock S. J., Paterson G. K. (2015). Mechanisms of Methicillin Resistance in Staphylococcus Aureus . Annu. Rev. Biochem. 84, 577–601. doi: 10.1146/annurev-biochem-060614-034516
    1. Pérez-Capilla T., Baquero M. R., Gómez-Gómez J. M., Ionel A., Martín S., Blázquez J. (2005). SOS-Independent Induction of dinB Transcription by Beta-Lactam-Mediated Inhibition of Cell Wall Synthesis in Escherichia Coli . J. Bacteriol. 187, 1515–1518. doi: 10.1128/JB.187.4.1515-1518.2005
    1. Peterson E., Kaur P. (2018). Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens. Front. Microbiol. 9, 2928. doi: 10.3389/fmicb.2018.02928
    1. Petrova V., Chitteni-Pattu S., Drees J. C., Inman R. B., Cox M. M. (2009). An SOS Inhibitor That Binds to Free RecA Protein: The PsiB Protein. Mol. Cell 36, 121–130. doi: 10.1016/j.molcel.2009.07.026
    1. Phillips I., Culebras E., Moreno F., Baquero F. (1987). Induction of the SOS Response by New 4-Quinolones. J. Antimicrob. Chemother. 20, 631–638. doi: 10.1093/jac/20.5.631
    1. Podlesek Z., Zgur Bertok D. (2020). The DNA Damage Inducible SOS Response is a Key Player in the Generation of Bacterial Persister Cells and Population Wide Tolerance. Front. Microbiol. 11, 1785. doi: 10.3389/fmicb.2020.01785
    1. Pomposiello P. J., Bennik M. H., Demple B. (2001). Genome-Wide Transcriptional Profiling of the Escherichia Coli Responses to Superoxide Stress and Sodium Salicylate. J. Bacteriol. 183, 3890–3902. doi: 10.1128/JB.183.13.3890-3902.2001
    1. Pomposiello P. J., Demple B. (2001). Redox-Operated Genetic Switches: The SoxR and OxyR Transcription Factors. Trends Biotechnol. 19, 109–114. doi: 10.1016/S0167-7799(00)01542-0
    1. Pontes M. H., Groisman E. A. (2019). Slow Growth Determines Nonheritable Antibiotic Resistance in Salmonella Enterica . Sci. Signal 12. doi: 10.1126/scisignal.aax3938
    1. Pontes M. H., Groisman E. A. (2020). A Physiological Basis for Nonheritable Antibiotic Resistance. mBio 11. doi: 10.1128/mBio.00817-20
    1. Poole K. (2011). Pseudomonas Aeruginosa: Resistance to the Max. Front. Microbiol. 2, 65. doi: 10.3389/fmicb.2011.00065
    1. Prax M., Bertram R. (2014). Metabolic Aspects of Bacterial Persisters. Front. Cell Infect. Microbiol. 4, 148. doi: 10.3389/fcimb.2014.00148
    1. Prudhomme M., Attaiech L., Sanchez G., Martin B., Claverys J. P. (2006). Antibiotic Stress Induces Genetic Transformability in the Human Pathogen Streptococcus Pneumoniae . Science 313, 89–92. doi: 10.1126/science.1127912
    1. Pu Y., Li Y., Jin X., Tian T., Ma Q., Zhao Z., et al. . (2019). ATP-Dependent Dynamic Protein Aggregation Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance. Mol. Cell 73, 143–156 e144. doi: 10.1016/j.molcel.2018.10.022
    1. Puzari M., Sharma M., Chetia P. (2018). Emergence of Antibiotic Resistant Shigella Species: A Matter of Concern. J. Infect. Public Health 11, 451–454. doi: 10.1016/j.jiph.2017.09.025
    1. Radman M. (1975). SOS Repair Hypothesis: Phenomenology of an Inducible DNA Repair Which is Accompanied by Mutagenesis. Basic Life Sci. 5A, 355–367. doi: 10.1007/978-1-4684-2895-7_48
    1. Radzikowski J. L., Schramke H., Heinemann M. (2017). Bacterial Persistence From a System-Level Perspective. Curr. Opin. Biotechnol. 46, 98–105. doi: 10.1016/j.copbio.2017.02.012
    1. Radzikowski J. L., Vedelaar S., Siegel D., Ortega A. D., Schmidt A., Heinemann M. (2016). Bacterial Persistence is an Active sigmaS Stress Response to Metabolic Flux Limitation. Mol. Syst. Biol. 12, 882. doi: 10.15252/msb.20166998
    1. Rakic-Martinez M., Drevets D. A., Dutta V., Katic V., Kathariou S. (2011). Listeria Monocytogenes Strains Selected on Ciprofloxacin or the Disinfectant Benzalkonium Chloride Exhibit Reduced Susceptibility to Ciprofloxacin, Gentamicin, Benzalkonium Chloride, and Other Toxic Compounds. Appl. Environ. Microbiol. 77, 8714–8721. doi: 10.1128/AEM.05941-11
    1. Ramirez M. S., Tolmasky M. E. (2010). Aminoglycoside Modifying Enzymes. Drug Resist. Update 13, 151–171. doi: 10.1016/j.drup.2010.08.003
    1. Randall L. P., Cooles S. W., Osborn M. K., Piddock L. J., Woodward M. J. (2004). Antibiotic Resistance Genes, Integrons and Multiple Antibiotic Resistance in Thirty-Five Serotypes of Salmonella Enterica Isolated From Humans and Animals in the UK. J. Antimicrob. Chemother. 53, 208–216. doi: 10.1093/jac/dkh070
    1. Rand L., Hinds J., Springer B., Sander P., Buxton R. S., Davis E. O. (2003). The Majority of Inducible DNA Repair Genes in Mycobacterium Tuberculosis are Induced Independently of RecA. Mol. Microbiol. 50, 1031–1042. doi: 10.1046/j.1365-2958.2003.03765.x
    1. Rasouly A., Nudler E. (2019). Reactive Oxygen Species as the Long Arm of Bactericidal Antibiotics. Proc. Natl. Acad. Sci. U.S.A. 116, 9696–9698. doi: 10.1073/pnas.1905291116
    1. Raychaudhury P., Basu A. K. (2011). Genetic Requirement for Mutagenesis of the G[8,5-Me]T Cross-Link in Escherichia Coli: DNA Polymerases IV and V Compete for Error-Prone Bypass. Biochemistry 50, 2330–2338. doi: 10.1021/bi102064z
    1. Regev T., Myers N., Zarivach R., Fishov I. (2012). Association of the Chromosome Replication Initiator DnaA With the Escherichia Coli Inner Membrane In Vivo: Quantity and Mode of Binding. PloS One 7, e36441. doi: 10.1371/journal.pone.0036441
    1. Riber L., Hansen L. H. (2021). Epigenetic Memories: The Hidden Drivers of Bacterial Persistence? Trends Microbiol. 29, 190–194. doi: 10.1016/j.tim.2020.12.005
    1. Robicsek A., Strahilevitz J., Jacoby G. A., Macielag M., Abbanat D., Park C. H., et al. . (2006). Fluoroquinolone-Modifying Enzyme: A New Adaptation of a Common Aminoglycoside Acetyltransferase. Nat. Med. 12, 83–88. doi: 10.1038/nm1347
    1. Rolain J. M., Fancello L., Desnues C., Raoult D. (2011). Bacteriophages as Vehicles of the Resistome in Cystic Fibrosis. J. Antimicrob. Chemother. 66, 2444–2447. doi: 10.1093/jac/dkr318
    1. Rolain J. M., Raoult D. (2005). Genome Comparison Analysis of Molecular Mechanisms of Resistance to Antibiotics in the Rickettsia Genus. Ann. N Y Acad. Sci. 1063, 222–230. doi: 10.1196/annals.1355.035
    1. Rosch J. W., Tuomanen E. I. (2020). Caging and COM-Bating Antibiotic Resistance. Cell Host Microbe 27, 489–490. doi: 10.1016/j.chom.2020.03.013
    1. Rowe S. E., Conlon B. P., Keren I., Lewis K. (2016). Persisters: Methods for Isolation and Identifying Contributing Factors - a Review. Methods Mol. Biol. 1333, 17–28. doi: 10.1007/978-1-4939-2854-5_2
    1. Rowe-Magnus D. A., Guerout A. M., Mazel D. (2002). Bacterial Resistance Evolution by Recruitment of Super-Integron Gene Cassettes. Mol. Microbiol. 43, 1657–1669. doi: 10.1046/j.1365-2958.2002.02861.x
    1. Rumbo C., Fernandez-Moreira E., Merino M., Poza M., Mendez J. A., Soares N. C., et al. . (2011). Horizontal Transfer of the OXA-24 Carbapenemase Gene via Outer Membrane Vesicles: A New Mechanism of Dissemination of Carbapenem Resistance Genes in Acinetobacter Baumannii . Antimicrob. Agents Chemother. 55, 3084–3090. doi: 10.1128/AAC.00929-10
    1. Rycroft J. A., Gollan B., Grabe G. J., Hall A., Cheverton A. M., Larrouy-Maumus G., et al. . (2018). Activity of Acetyltransferase Toxins Involved in Salmonella Persister Formation During Macrophage Infection. Nat. Commun. 9, 1993. doi: 10.1038/s41467-018-04472-6
    1. Salcedo-Sora J. E., Kell D. B. (2020). A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery. Antibiot. (Basel) 9. doi: 10.3390/antibiotics9080508
    1. Salverda M. L., De Visser J. A., Barlow M. (2010). Natural Evolution of TEM-1 Beta-Lactamase: Experimental Reconstruction and Clinical Relevance. FEMS Microbiol. Rev. 34, 1015–1036. doi: 10.1111/j.1574-6976.2010.00222.x
    1. Samadpour A. N., Merrikh H. (2018). DNA Gyrase Activity Regulates DnaA-Dependent Replication Initiation in Bacillus Subtilis . Mol. Microbiol. 108, 115–127. doi: 10.1111/mmi.13920
    1. Sandoz K. M., Rockey D. D. (2010). Antibiotic Resistance in Chlamydiae. Future Microbiol. 5, 1427–1442. doi: 10.2217/fmb.10.96
    1. Schenk K., Hervas A. B., Rösch T. C., Eisemann M., Schmitt B. A., Dahlke S., et al. . (2017). Rapid Turnover of DnaA at Replication Origin Regions Contributes to Initiation Control of DNA Replication. PloS Genet. 13, e1006561. doi: 10.1371/journal.pgen.1006561
    1. Schlüter A., Szczepanowski R., Kurz N., Schneiker S., Krahn I., Puhler A. (2007). Erythromycin Resistance-Conferring Plasmid Prsb105, Isolated From a Sewage Treatment Plant, Harbors a New Macrolide Resistance Determinant, an Integron-Containing Tn402-Like Element, and a Large Region of Unknown Function. Appl. Environ. Microbiol. 73, 1952–1960. doi: 10.1128/AEM.02159-06
    1. Schröder W., Goerke C., Wolz C. (2013). Opposing Effects of Aminocoumarins and Fluoroquinolones on the SOS Response and Adaptability in Staphylococcus Aureus . J. Antimicrob. Chemother. 68, 529–538. doi: 10.1093/jac/dks456
    1. Sebastian J., Swaminath S., Nair R. R., Jakkala K., Pradhan A., Ajitkumar P. (2017). De Novo Emergence of Genetically Resistant Mutants of Mycobacterium Tuberculosis From the Persistence Phase Cells Formed Against Antituberculosis Drugs In Vitro . Antimicrob. Agents Chemother. 61. doi: 10.1128/AAC.01343-16
    1. Sekiguchi M., Tsuzuki T. (2002). Oxidative Nucleotide Damage: Consequences and Prevention. Oncogene 21, 8895–8904. doi: 10.1038/sj.onc.1206023
    1. Serio A. W., Magalhães M. L., Blanchard J. S., Connolly L. E. (2017). “"Aminoglycosides: Mechanisms of Action and Resistance,",” in Antimicrobial Drug Resistance: Mechanisms of Drug Resistance, vol. Volume 1 . Eds. Mayers D. L., Sobel J. D., Ouellette M., Kaye K. S., Marchaim D. (Cham: Springer International Publishing; ), 213–229.
    1. Shadoud L., Almahmoud I., Jarraud S., Etienne J., Larrat S., Schwebel C., et al. . (2015). Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella Pneumophila and Humans. EBioMedicine 2, 1179–1185. doi: 10.1016/j.ebiom.2015.07.018
    1. Shan Y., Brown Gandt A., Rowe S. E., Deisinger J. P., Conlon B. P., Lewis K. (2017). ATP-Dependent Persister Formation in Escherichia Coli . mBio 8. doi: 10.1128/mBio.02267-16
    1. Shevtsov A., Syzdykov M., Kuznetsov A., Shustov A., Shevtsova E., Berdimuratova K., et al. . (2017). Antimicrobial Susceptibility of Brucella Melitensis in Kazakhstan. Antimicrob. Resist. Infect. Control 6, 130. doi: 10.1186/s13756-017-0293-x
    1. Siebert C., Lindgren H., Ferre S., Villers C., Boisset S., Perard J., et al. . (2019). Francisella Tularensis: FupA Mutation Contributes to Fluoroquinolone Resistance by Increasing Vesicle Secretion and Biofilm Formation. Emerg. Microbes Infect. 8, 808–822. doi: 10.1080/22221751.2019.1615848
    1. Simmons L. A., Foti J. J., Cohen S. E., Walker G. C. (2008). The SOS Regulatory Network. EcoSal. Plus. 3. doi: 10.1128/ecosal.5.4.3
    1. Slager J., Kjos M., Attaiech L., Veening J. W. (2014). Antibiotic-Induced Replication Stress Triggers Bacterial Competence by Increasing Gene Dosage Near the Origin. Cell 157, 395–406. doi: 10.1016/j.cell.2014.01.068
    1. Sommer S., Knezevic J., Bailone A., Devoret R. (1993). Induction of Only One SOS Operon, umuDC, is Required for SOS Mutagenesis in Escherichia Coli . Mol. Gen. Genet. 239, 137–144. doi: 10.1007/BF00281612
    1. Spoering A. L., Vulic M., Lewis K. (2006). GlpD and PlsB Participate in Persister Cell Formation in Escherichia Coli . J. Bacteriol. 188, 5136–5144. doi: 10.1128/JB.00369-06
    1. Stalder T., Barraud O., Casellas M., Dagot C., Ploy M. C. (2012). Integron Involvement in Environmental Spread of Antibiotic Resistance. Front. Microbiol. 3, 119. doi: 10.3389/fmicb.2012.00119
    1. Stamm L. V. (2015). Syphilis: Antibiotic Treatment and Resistance. Epidemiol. Infect. 143, 1567–1574. doi: 10.1017/S0950268814002830
    1. Sulaiman J. E., Lam H. (2021). Evolution of Bacterial Tolerance Under Antibiotic Treatment and its Implications on the Development of Resistance. Front. Microbiol. 12, 617412. doi: 10.3389/fmicb.2021.617412
    1. Tang S. S., Apisarnthanarak A., Hsu L. Y. (2014). Mechanisms of Beta-Lactam Antimicrobial Resistance and Epidemiology of Major Community- and Healthcare-Associated Multidrug-Resistant Bacteria. Adv. Drug Delivery Rev. 78, 3–13. doi: 10.1016/j.addr.2014.08.003
    1. Tang M., Pham P., Shen X., Taylor J. S., O'donnell M., Woodgate R., et al. . (2000). Roles of E. Coli DNA Polymerases IV and V in Lesion-Targeted and Untargeted SOS Mutagenesis. Nature 404, 1014–1018. doi: 10.1038/35010020
    1. Tan K. W., Pham T. M., Furukohri A., Maki H., Akiyama M. T. (2015). Recombinase and Translesion DNA Polymerase Decrease the Speed of Replication Fork Progression During the DNA Damage Response in Escherichia Coli Cells. Nucleic Acids Res. 43, 1714–1725. doi: 10.1093/nar/gkv044
    1. Tapsall J. W. (2005). Antibiotic Resistance in Neisseria Gonorrhoeae . Clin. Infect. Dis. 41 Suppl 4, S263–S268. doi: 10.1086/430787
    1. Tegova R., Tover A., Tarassova K., Tark M., Kivisaar M. (2004). Involvement of Error-Prone DNA Polymerase IV in Stationary-Phase Mutagenesis in Pseudomonas Putida . J. Bacteriol. 186, 2735–2744. doi: 10.1128/JB.186.9.2735-2744.2004
    1. Thomas C. M., Nielsen K. M. (2005). Mechanisms of, and Barriers to, Horizontal Gene Transfer Between Bacteria. Nat. Rev. Microbiol. 3, 711–721. doi: 10.1038/nrmicro1234
    1. Timinskas K., Venclovas C. (2019). New Insights Into the Structures and Interactions of Bacterial Y-Family DNA Polymerases. Nucleic Acids Res. 47, 4393–4405. doi: 10.1093/nar/gkz198
    1. Toyofuku M., Nomura N., Eberl L. (2019). Types and Origins of Bacterial Membrane Vesicles. Nat. Rev. Microbiol. 17, 13–24. doi: 10.1038/s41579-018-0112-2
    1. Tran F., Boedicker J. Q. (2017). Genetic Cargo and Bacterial Species Set the Rate of Vesicle-Mediated Horizontal Gene Transfer. Sci. Rep. 7, 8813. doi: 10.1038/s41598-017-07447-7
    1. Trastoy R., Manso T., Fernandez-Garcia L., Blasco L., Ambroa A., Perez Del Molino M. L., et al. . (2018). Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments. Clin. Microbiol. Rev. 31. doi: 10.1128/CMR.00023-18
    1. Trojanowski D., Holowka J., Zakrzewska-Czerwinska J. (2018). Where and When Bacterial Chromosome Replication Starts: A Single Cell Perspective. Front. Microbiol. 9, 2819. doi: 10.3389/fmicb.2018.02819
    1. Unemo M., Shafer W. M. (2014). Antimicrobial Resistance in Neisseria Gonorrhoeae in the 21st Century: Past, Evolution, and Future. Clin. Microbiol. Rev. 27, 587–613. doi: 10.1128/CMR.00010-14
    1. Van Acker H., Coenye T. (2017). The Role of Reactive Oxygen Species in Antibiotic-Mediated Killing of Bacteria. Trends Microbiol. 25, 456–466. doi: 10.1016/j.tim.2016.12.008
    1. Vanrompay D., Nguyen T. L. A., Cutler S. J., Butaye P. (2018). Antimicrobial Resistance in Chlamydiales, Rickettsia, Coxiella, and Other Intracellular Pathogens. Microbiol. Spectr. 6. doi: 10.1128/9781555819804.ch23
    1. Varga M., Kuntova L., Pantucek R., Maslanova I., Ruzickova V., Doskar J. (2012). Efficient Transfer of Antibiotic Resistance Plasmids by Transduction Within Methicillin-Resistant Staphylococcus Aureus USA300 Clone. FEMS Microbiol. Lett. 332, 146–152. doi: 10.1111/j.1574-6968.2012.02589.x
    1. Virolle C., Goldlust K., Djermoun S., Bigot S., Lesterlin C. (2020). Plasmid Transfer by Conjugation in Gram-Negative Bacteria: From the Cellular to the Community Level. Genes (Basel) 11. doi: 10.3390/genes11111239
    1. Vogwill T., Comfort A. C., Furio V., Maclean R. C. (2016). Persistence and Resistance as Complementary Bacterial Adaptations to Antibiotics. J. Evol. Biol. 29, 1223–1233. doi: 10.1111/jeb.12864
    1. Völzing K. G., Brynildsen M. P. (2015). Stationary-Phase Persisters to Ofloxacin Sustain DNA Damage and Require Repair Systems Only During Recovery. mBio 6, e00731–e00715. doi: 10.1128/mBio.00731-15
    1. Von Wintersdorff C. J., Penders J., Van Niekerk J. M., Mills N. D., Majumder S., Van Alphen L. B., et al. . (2016). Dissemination of Antimicrobial Resistance in Microbial Ecosystems Through Horizontal Gene Transfer. Front. Microbiol. 7, 173. doi: 10.3389/fmicb.2016.00173
    1. Voth D. E., Heinzen R. A. (2007). Lounging in a Lysosome: The Intracellular Lifestyle of Coxiella Burnetii . Cell Microbiol. 9, 829–840. doi: 10.1111/j.1462-5822.2007.00901.x
    1. Vranakis I., De Bock P. J., Papadioti A., Samoilis G., Tselentis Y., Gevaert K., et al. . (2011). Unraveling Persistent Host Cell Infection With Coxiella Burnetii by Quantitative Proteomics. J. Proteome Res. 10, 4241–4251. doi: 10.1021/pr200422f
    1. Wain J., Diem Nga L. T., Kidgell C., James K., Fortune S., Song Diep T., et al. . (2003). Molecular Analysis of Inchi1 Antimicrobial Resistance Plasmids From Salmonella Serovar Typhi Strains Associated With Typhoid Fever. Antimicrob. Agents Chemother. 47, 2732–2739. doi: 10.1128/AAC.47.9.2732-2739.2003
    1. Walker G. C. (1984). Mutagenesis and Inducible Responses to Deoxyribonucleic Acid Damage in Escherichia Coli . Microbiol. Rev. 48, 60–93. doi: 10.1128/mr.48.1.60-93.1984
    1. Wattam A. R., Williams K. P., Snyder E. E., Almeida N. F., Jr., Shukla M., Dickerman A. W., et al. . (2009). Analysis of Ten Brucella Genomes Reveals Evidence for Horizontal Gene Transfer Despite a Preferred Intracellular Lifestyle. J. Bacteriol. 191, 3569–3579. doi: 10.1128/JB.01767-08
    1. Weigand M. R., Sundin G. W. (2012). General and Inducible Hypermutation Facilitate Parallel Adaptation in Pseudomonas Aeruginosa Despite Divergent Mutation Spectra. Proc. Natl. Acad. Sci. U.S.A. 109, 13680–13685. doi: 10.1073/pnas.1205357109
    1. Westblade L. F., Errington J., Dörr T. (2020). Antibiotic Tolerance. PloS Pathog. 16, e1008892. doi: 10.1371/journal.ppat.1008892
    1. White P. A., Mciver C. J., Rawlinson W. D. (2001). Integrons and Gene Cassettes in the Enterobacteriaceae. Antimicrob. Agents Chemother. 45, 2658–2661. doi: 10.1128/AAC.45.9.2658-2661.2001
    1. Wilson D. N. (2014). Ribosome-Targeting Antibiotics and Mechanisms of Bacterial Resistance. Nat. Rev. Microbiol. 12, 35–48. doi: 10.1038/nrmicro3155
    1. Windels E. M., Michiels J. E., Fauvart M., Wenseleers T., Van Den Bergh B., Michiels J. (2019). Bacterial Persistence Promotes the Evolution of Antibiotic Resistance by Increasing Survival and Mutation Rates. ISME J. 13, 1239–1251. doi: 10.1038/s41396-019-0344-9
    1. Woodford N., Ellington M. J. (2007). The Emergence of Antibiotic Resistance by Mutation. Clin. Microbiol. Infect. 13, 5–18. doi: 10.1111/j.1469-0691.2006.01492.x
    1. Wozniak K. J., Simmons L. A. (2022). Bacterial DNA Excision Repair Pathways. Nat. Rev. Microbiol. doi: 10.1038/s41579-022-00694-0
    1. Wright G. D. (2007). The Antibiotic Resistome: The Nexus of Chemical and Genetic Diversity. Nat. Rev. Microbiol. 5, 175–186. doi: 10.1038/nrmicro1614
    1. Wright G. D. (2010). Antibiotic Resistance in the Environment: A Link to the Clinic? Curr. Opin. Microbiol. 13, 589–594. doi: 10.1016/j.mib.2010.08.005
    1. Wright H., Bonomo R. A., Paterson D. L. (2017). New Agents for the Treatment of Infections With Gram-Negative Bacteria: Restoring the Miracle or False Dawn? Clin. Microbiol. Infect. 23, 704–712. doi: 10.1016/j.cmi.2017.09.001
    1. Wu Y., Vulic M., Keren I., Lewis K. (2012). Role of Oxidative Stress in Persister Tolerance. Antimicrob. Agents Chemother. 56, 4922–4926. doi: 10.1128/AAC.00921-12
    1. Xu Y., Liu S., Zhang Y., Zhang W. (2021). DNA Adenine Methylation is Involved in Persister Formation in E. Coli . Microbiol. Res. 246, 126709. doi: 10.1016/j.micres.2021.126709
    1. Yamanaka K., Chatterjee N., Hemann M. T., Walker G. C. (2017). Inhibition of Mutagenic Translesion Synthesis: A Possible Strategy for Improving Chemotherapy? PloS Genet. 13, e1006842. doi: 10.1371/journal.pgen.1006842
    1. Yang W. (2014). An Overview of Y-Family DNA Polymerases and a Case Study of Human DNA Polymerase Eta. Biochemistry 53, 2793–2803. doi: 10.1021/bi500019s
    1. Yang J. H., Bhargava P., Mccloskey D., Mao N., Palsson B. O., Collins J. J. (2017). Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function. Cell Host Microbe 22, 757–765 e753. doi: 10.1016/j.chom.2017.10.020
    1. Yang W., Gao Y. (2018). Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism. Annu. Rev. Biochem. 87, 239–261. doi: 10.1146/annurev-biochem-062917-012405
    1. Yang Q. E., Walsh T. R. (2017). Toxin-Antitoxin Systems and Their Role in Disseminating and Maintaining Antimicrobial Resistance. FEMS Microbiol. Rev. 41, 343–353. doi: 10.1093/femsre/fux006
    1. Zampieri M., Zimmermann M., Claassen M., Sauer U. (2017). Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic Perturbations. Cell Rep. 19, 1214–1228. doi: 10.1016/j.celrep.2017.04.002
    1. Zankari E., Hasman H., Cosentino S., Vestergaard M., Rasmussen S., Lund O., et al. . (2012). Identification of Acquired Antimicrobial Resistance Genes. J. Antimicrob. Chemother. 67, 2640–2644. doi: 10.1093/jac/dks261
    1. Zhang Y., Gu A. Z., Cen T., Li X., He M., Li D., et al. . (2018). Sub-Inhibitory Concentrations of Heavy Metals Facilitate the Horizontal Transfer of Plasmid-Mediated Antibiotic Resistance Genes in Water Environment. Environ. pollut. 237, 74–82. doi: 10.1016/j.envpol.2018.01.032
    1. Zhang Y. J., Li X. J., Mi K. X. (2016). Mechanisms of Fluoroquinolone Resistance in Mycobacterium Tuberculosis . Yi Chuan 38, 918–927. doi: 10.16288/j.yczz.16-136
    1. Zhao X., Drlica K. (2014). Reactive Oxygen Species and the Bacterial Response to Lethal Stress. Curr. Opin. Microbiol. 21, 1–6. doi: 10.1016/j.mib.2014.06.008
    1. Zhao X., Hong Y., Drlica K. (2015). Moving Forward With Reactive Oxygen Species Involvement in Antimicrobial Lethality. J. Antimicrob. Chemother. 70, 639–642. doi: 10.1093/jac/dku463
    1. Zheng M., Doan B., Schneider T. D., Storz G. (1999). OxyR and SoxRS Regulation of Fur . J. Bacteriol. 181, 4639–4643. doi: 10.1128/JB.181.15.4639-4643.1999
    1. Zhou H., Beltran J. F., Brito I. L. (2021). Functions Predict Horizontal Gene Transfer and the Emergence of Antibiotic Resistance. Sci. Adv. 7, eabj5056. doi: 10.1126/sciadv.abj5056
    1. Zou J., Kou S. H., Xie R., Vannieuwenhze M. S., Qu J., Peng B., et al. . (2020). Non-Walled Spherical Acinetobacter Baumannii is an Important Type of Persister Upon Beta-Lactam Antibiotic Treatment. Emerg. Microbes Infect. 9, 1149–1159. doi: 10.1080/22221751.2020.1770630
    1. Zwama M., Nishino K. (2021). Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race Against Time. Antibiot. (Basel) 10. doi: 10.3390/antibiotics10070774

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