Population genetic analysis of Propionibacterium acnes identifies a subpopulation and epidemic clones associated with acne

Hans B Lomholt, Mogens Kilian, Hans B Lomholt, Mogens Kilian

Abstract

The involvement of Propionibacterium acnes in the pathogenesis of acne is controversial, mainly owing to its dominance as an inhabitant of healthy skin. This study tested the hypothesis that specific evolutionary lineages of the species are associated with acne while others are compatible with health. Phylogenetic reconstruction based on nine housekeeping genes was performed on 210 isolates of P. acnes from well-characterized patients with acne, various opportunistic infections, and from healthy carriers. Although evidence of recombination was observed, the results showed a basically clonal population structure correlated with allelic variation in the virulence genes tly and camp5, with pulsed field gel electrophoresis (PFGE)- and biotype, and with expressed putative virulence factors. An unexpected geographically and temporal widespread dissemination of some clones was demonstrated. The population comprised three major divisions, one of which, including an epidemic clone, was strongly associated with moderate to severe acne while others were associated with health and opportunistic infections. This dichotomy correlated with previously observed differences in in vitro inflammation-inducing properties. Comparison of five genomes representing acne- and health-associated clones revealed multiple both cluster- and strain-specific genes that suggest major differences in ecological preferences and redefines the spectrum of disease-associated virulence factors. The results of the study indicate that particular clones of P. acnes play an etiologic role in acne while others are associated with health.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Population structure of P. acnes…
Figure 1. Population structure of P. acnes.
Minimum evolution tree of 57 sequence types (ST) detected among 210 isolates of P. acnes from skin of healthy individuals, from patients with varying degrees of acne, and from other infectious diseases. The majority of isolates were from Caucasians. Isolates from healthy Chinese individuals are indicated by an asterix. The number of independent isolates assigned to each ST containing more than one isolate is shown in brackets. Each isolate from cases of severe acne is indicated by a filled black circle and isolates from infections in normally sterile tissues and blood are indicated by an open red circle. The correlation of clusters with biotype, PFGE type, and tly and camp5 alleles is shown to the right. The bar represents the genetic distance.
Figure 2. Population snapshot of P. acnes…
Figure 2. Population snapshot of P. acnes identifies a limited number of clone complexes with founders.
The eBURST analysis of the allele profile in nine housekeeping and two virulence genes in 143 independent P. acnes strains identified eight clusters. Connected members of clusters differed by only one allele out of 11 loci and are assumed to be descended from the same founding genotype. The area of the black circles reflect the number of isolates (see also Figure 1) and the area of the red circles reflect the number of isolates from severe acne. The ST18 cluster included 46 isolates, 14 (30%) of which were from severe acne, whereas the other major cluster, the ST36 cluster, included 23 isolates, one (4.3%) of which was from severe acne. Occasional strains that deviated from the majority allele profile of a certain ST in a single virulence gene are indicated by an A added to the ST number. The founders of the three major ST18, ST36, and ST53 clusters were supported by a bootstrap value of 99, 99, and 78%, respectively.
Figure 3. Certain epidemic clones and subpopulations…
Figure 3. Certain epidemic clones and subpopulations of P. acnes are associated with severe acne and soft tissue infections.
Percentage of prospectively collected Danish isolates from patients with moderate to severe acne (black bars) versus isolates from healthy controls (grey bars) in A), division I-1 compared to divisions I-2 and II combined; B), ST 27 compared to the rest of division I-1 among Danish isolates; and C), percentage of isolates from blood and infections in normally sterile tissues (see table S4 for details) for division I-1 compared to divisions I-2, II and III among all 143 non-redundant strains included.
Figure 4. Assignment of genome sequenced strains…
Figure 4. Assignment of genome sequenced strains and relevant collection strains to phylogenetic clusters within P. acnes.

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