糖尿病患者の足の創傷および骨炎におけるブドウ球菌ペッテンコフェリの病原性因子 (PETTENK-OS)
糖尿病患者の足の創傷および骨炎におけるブドウ球菌ペッテンコフェリの病原性因子の評価。 PETTENK-OS 研究
Gram-positive cocci, particularly Staphylococcus aureus and coagulase-negative staphylococci (SCoN), are the bacteria most frequently isolated from diabetic foot ulcers. Although studies have been carried out on the role of S. aureus in the unfavorable evolution of these wounds, no studies have focused on the role of SCoN. Of the fifty or so SCoN species, not all have the same virulence potential. The role of Staphylococcus pettenkoferi is unknown, yet this bacterium is the 7th most frequently identified in diabetic foot ulcers, suggesting that it may also be involved in the pathophysiology of these infections. At Nîmes University Hospital, this bacterium is mainly identified in samples from diabetic foot ulcers or osteitis in our laboratory and 80% of the bacteria present are in biofilms.It is essential to understand the mechanisms governing these bacterial interactions and establish the true pathogenic potential of these bacteria. Recently, the Nîmes team showed that a strain of S. pettenkoferi (SP165) isolated from foot osteitis in a diabetic patient had real virulence potential. SP165 could not only produce biofilm, but could also survive in human blood, human keratinocytes and murine and human macrophages. It also caused significant embryonic mortality in a zebrafish model. A second study of 29 isolates from Nîmes University Hospital subsequently demonstrated that there were two predominant clones with different virulences. Three biofilm production profiles (rapidly and highly biofilm-producing, slowly biofilm-producing and non-biofilm-producing) and two zebrafish profiles (highly and moderately lethal) were reported by phenotypic and genomic analyses on this panel of strains. Genes for resistance, virulence and biofilm production were also found on their genomes.
調査の概要
状態
条件
介入・治療
- 他の：Molecular epidemiology of the collection
- 他の：Study of the resistome of the S. pettenkoferi population
- 他の：Study of the virulome of the S. pettenkoferi population
- 他の：Study of the resistance profiles of all S. pettenkoferi isolates
- 他の：Selection of strains for in-depth phenotypic study
- 他の：Selection of strains (n=3) for the virulence study
詳細な説明
Gram-positive cocci, in particular Staphylococcus aureus and coagulase-negative staphylococci (SCoN), are the bacteria most frequently isolated from diabetic foot ulcers. While studies have been carried out on the role of S. aureus in the unfavorable evolution of these wounds, no study has focused on the role of SCoN. Of the fifty or so SCoN species, not all have the same virulence potential. The role of Staphylococcus pettenkoferi is not known. Yet this bacterium is the 7th most frequently identified in diabetic foot ulcers, suggesting that it may also be involved in the pathophysiology of these infections. In the work of Loetsche et al. a study of the microbiome of 349 diabetic foot ulcer samples by targeted 16S rDNA sequencing showed that the genus Staphylococcus was the most abundant, with a relative abundance of 22.8%, including 13.3% S. aureus and 5.3% S. pettenkoferi.
At Nîmes University Hospital, this bacterium is mainly identified in samples from diabetic foot ulcers or osteitis in our laboratory (89 isolations of S. pettenkoferi from diabetic foot ulcer samples out of 167 isolations made of this bacterium between 2018 and 2022).The difficulty of managing chronic wounds also lies in the fact that almost 80% of the bacteria present are in biofilms. It has also been established that the environment in which bacteria are found, and in particular the interactions they establish between themselves, play a significant role in delayed wound healing. It is therefore essential to understand the mechanisms governing these bacterial interactions and to establish the true pathogenic potential of these bacteria.
Recently, our team demonstrated that a strain of S. pettenkoferi (SP165) isolated from foot osteitis in a diabetic patient had real virulence potential. As well as being able to produce biofilm, SP165 was able to survive in human blood, human keratinocytes and murine and human macrophages. It also demonstrated its virulence by causing significant embryonic mortality in the zebrafish model.
A second study of 29 isolates from Nîmes University Hospital subsequently demonstrated the existence of two predominant clones with different virulences.
Three biofilm production profiles (rapidly and highly biofilm-producing, slowly biofilm-producing and non-biofilm-producing) and two zebrafish virulence profiles (highly and moderately lethal) were reported by phenotypic and genomic analyses on this panel of strains. Genes for resistance, virulence and biofilm production were also found on their genomes.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Gard
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Nîmes、Gard、フランス、30029
- Nîmes University Hospital
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
The collection of strains at the Nîmes University Hospital site from 9 European laboratories collected between 2015 and 2023 for a total of 108 months was carried out between November 2021 and August 2023.
説明
Inclusion Criteria:
- Not applicable for this research on a ready-constituted collection of strains of Staphylococcus pettenkoferi
Exclusion Criteria:
- Not applicable for this research on a ready-constituted collection of strains of Staphylococcus pettenkoferi
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：COHORT
- 時間の展望：OTHER
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Genetic diversity of Staphyloccocus pettenkoferi strains isolated from osteitis and non-diabetic wounds, blood cultures and nasal carriage.
時間枠：Day 0 to 3 months
|
Number of clades estimated via typing by complete sequencing of the bacterial genomes of all S. pettenkoferi strains and analysis of phylogenetic distances (whole genome and core genome single nucleotide polymorphisms). |
Day 0 to 3 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Genetic diversity of Staphyloccocus pettenkoferi strains isolated from osteitis and non-diabetic wounds, blood cultures and nasal carriage.
時間枠：3 - 6 months
|
Number of clades estimated via typing by complete sequencing of the bacterial genomes of all Staphylococcus pettenkoferi strains and analysis of phylogenetic distances. |
3 - 6 months
|
|
Resistome in the strain population according to sample origin:osteitis
時間枠：3 - 6 months
|
The presence of antibiotic resistance genes (resistome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Resistome in the strain population according to sample origin: non-diabetic wounds
時間枠：3 - 6 months
|
The presence of antibiotic resistance genes (resistome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Resistome in the strain population according to sample origin: diabetic wounds
時間枠：3 - 6 months
|
The presence of antibiotic resistance genes (resistome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Resistome in the strain population according to sample origin: blood cultures
時間枠：3 - 6 months
|
The presence of antibiotic resistance genes (resistome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Resistome in the strain population according to sample origin: nasal carriage
時間枠：3 - 6 months
|
The presence of antibiotic resistance genes (resistome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Virulome in the strain population according to sample origin: osteitis
時間枠：3 - 6 months
|
The presence of virulence genes (virulome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Virulome in the strain population according to sample origin: non-diabetic wounds
時間枠：3 - 6 months
|
The presence of virulence genes (virulome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Virulome in the strain population according to sample origin: diabetic wounds
時間枠：3 - 6 months
|
The presence of virulence genes (virulome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Virulome in the strain population according to sample origin: blood cultures
時間枠：3 - 6 months
|
The presence of virulence genes (virulome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Virulome in the strain population according to sample origin: nasal carriage
時間枠：3 - 6 months
|
The presence of virulence genes (virulome) will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Plasmids inthe strain population and according to sample origin: osteitis
時間枠：3 - 6 months
|
The presence of plasmids will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Plasmids inthe strain population and according to sample origin: non-diabetic wounds
時間枠：3 - 6 months
|
The presence of plasmids will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Plasmids inthe strain population and according to sample origin: diabetic wounds
時間枠：3 - 6 months
|
The presence of plasmids will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Plasmids inthe strain population and according to sample origin: blood cultures
時間枠：3 - 6 months
|
The presence of plasmids will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Plasmids inthe strain population and according to sample origin: nasal carriage
時間枠：3 - 6 months
|
The presence of plasmids will be identified by bioinformatics analysis of sequenced bacterial genomes. |
3 - 6 months
|
|
Phenotypic resistance profiles in the population in a subsample of 85 strains
時間枠：6 - 14 months
|
The minimum inhibitory concentration for a series of antibiotics will be recorded (antibiograms of isolates).These antibiograms will be established on newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. |
6 - 14 months
|
|
Phenotypic resistance profiles in the population and according to sample origin: osteitis
時間枠：6 - 14 months
|
Minimum inhibitory concentration for a series of antibiotics (antibiograms of isolates). These antibiograms will be established on newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. |
6 - 14 months
|
|
Phenotypic resistance profiles in the population and according to sample origin: non-diabetic wounds
時間枠：6 - 14 months
|
Minimum inhibitory concentration for a series of antibiotics (antibiograms of isolates). These antibiograms will be established on newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. |
6 - 14 months
|
|
Phenotypic resistance profiles in the population and according to sample origin: diabetic wounds
時間枠：6 - 14 months
|
Minimum inhibitory concentration for a series of antibiotics (antibiograms of isolates). These antibiograms will be established on newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. |
6 - 14 months
|
|
Phenotypic resistance profiles in the population and according to sample origin: blood cultures
時間枠：6 - 14 months
|
Minimum inhibitory concentration for a series of antibiotics (antibiograms of isolates). These antibiograms will be established on newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. |
6 - 14 months
|
|
Phenotypic resistance profiles in the population and according to sample origin: nasal carriage
時間枠：6 - 14 months
|
Minimum inhibitory concentration for a series of antibiotics (antibiograms of isolates). These antibiograms will be established on newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. |
6 - 14 months
|
|
Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: osteitis
時間枠：6 - 14 months
|
Biofilm formation index in the presence/absence of a series of antibiotics (antibiograms of isolates). These antibiotics will be newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. Results recorded on a scale ranging from 0 = biofilm and 12 = no biofilm |
6 - 14 months
|
|
Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: non-diabetic wounds
時間枠：6 - 14 months
|
Biofilm formation index in the presence/absence of a series of antibiotics (antibiograms of isolates). These antibiotics will be newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. Results recorded on a scale ranging from 0 = biofilm and 12 = no biofilm |
6 - 14 months
|
|
Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: diabetic wounds
時間枠：6 - 14 months
|
Biofilm formation index in the presence/absence of a series of antibiotics (antibiograms of isolates). These antibiotics will be newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. Results recorded on a scale ranging from 0 = biofilm and 12 = no biofilm |
6 - 14 months
|
|
Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: blood cultures
時間枠：6 - 14 months
|
Biofilm formation index in the presence/absence of a series of antibiotics (antibiograms of isolates). These antibiotics will be newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. Results recorded on a scale ranging from 0 = biofilm and 12 = no biofilm |
6 - 14 months
|
|
Amount of biofilm formation in the absence and presence of antibiotics in a selection (85 sub-samples) of S. pettenkoferi strains according to sample origine: nasal carriage
時間枠：6 - 14 months
|
Biofilm formation index in the presence/absence of a series of antibiotics (antibiograms of isolates). These antibiotics will be newly-marketed or current molecules such as Ceftarolin, Ceftobiprol, Dalbavancin, Delafloxacin, Tedizolid and Oritavancin. Results recorded on a scale ranging from 0 = biofilm and 12 = no biofilm |
6 - 14 months
|
|
Bacterial growth rate according to sample origin in a sub-sample of 20 strains: osteitis
時間枠：6 - 14 months
|
Bacterial growth curve by measuring absorbance on bacterial culture over time. |
6 - 14 months
|
|
Bacterial growth rate according to sample origin in a sub-sample of 20 strains: non-diabetic wounds
時間枠：6 - 14 months
|
Bacterial growth curve by measuring absorbance on bacterial culture over time. |
6 - 14 months
|
|
Bacterial growth rate according to sample origin in a sub-sample of 20 strains: diabetic wounds
時間枠：6 - 14 months
|
Bacterial growth curve by measuring absorbance on bacterial culture over time. |
6 - 14 months
|
|
Bacterial growth rate according to sample origin in a sub-sample of 20 strains: blood cultures
時間枠：6 - 14 months
|
Bacterial growth curve by measuring absorbance on bacterial culture over time. |
6 - 14 months
|
|
Bacterial growth rate according to sample origin in a sub-sample of 20 strains: nasal carriage
時間枠：6 - 14 months
|
Bacterial growth curve by measuring absorbance on bacterial culture over time. |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: osteitis
時間枠：6 - 14 months
|
The rate of internalisation and release of LDH (a sign of cellular toxicity of the bacterial isolate) in an in vitro osteoblast cell culture model (MC3T3-E1) |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: intracellular bacterial multiplication of S. pettenkoferi strains from osteitis
時間枠：6 - 14 months
|
The amount of intracellular bacterial multiplication will be assessed in an in vitro macrophage cell culture model (RAW 264.7). |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: diabetic wounds
時間枠：6 - 14 months
|
The rate of internalisation and release of LDH (a sign of cellular toxicity of the bacterial isolate) in an in vitro osteoblast cell culture model (MC3T3-E1) |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: intracellular bacterial multiplication of S. pettenkoferi strains from diabetic wounds
時間枠：6 - 14 months
|
The amount of intracellular bacterial multiplication will be assessed in an in vitro macrophage cell culture model (RAW 264.7). |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: blood cultures
時間枠：6 - 14 months
|
The rate of internalisation and release of LDH (a sign of cellular toxicity of the bacterial isolate) in an in vitro osteoblast cell culture model (MC3T3-E1) |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains:intracellular bacterial multiplication of S. pettenkoferi strains from blood cultures
時間枠：6 - 14 months
|
The amount of intracellular bacterial multiplication will be assessed in an in vitro macrophage cell culture model (RAW 264.7). |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: nasal carriage
時間枠：6 - 14 months
|
The rate of internalisation and release of LDH (a sign of cellular toxicity of the bacterial isolate) in an in vitro osteoblast cell culture model (MC3T3-E1) |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains:intracellular bacterial multiplication of S. pettenkoferi strains from nasal carriage
時間枠：6 - 14 months
|
The amount of intracellular bacterial multiplication will be assessed in an in vitro macrophage cell culture model (RAW 264.7). |
6 - 14 months
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from osteitis
時間枠：Up to 48 hours
|
Survival curve at 48 hours |
Up to 48 hours
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from non-diabetic wounds
時間枠：Up to 48 hours
|
Survival curve at 48 hours |
Up to 48 hours
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from diabetic wounds
時間枠：Up to 48 hours
|
Survival curve at 48 hours |
Up to 48 hours
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from blood cultures
時間枠：Up to 48 hours
|
Survival curve at 48 hours |
Up to 48 hours
|
|
Virulence profiles according to sample origin in a sub-sample of 3 strains: survival time of diabetic zebrafish immersed in S. pettenkoferi strains from nasal carriage
時間枠：Up to 48 hours
|
Survival curve at 48 hours |
Up to 48 hours
|
協力者と研究者
協力者
捜査官
- 主任研究者：Chloé MAGNAN, Dr.、Nîmes University Hospital, FRANCE
出版物と役立つリンク
一般刊行物
- Magnan C, Curtil-Dit-Galin M, Morsli M, Cattoir V, Piau-Couapel C, Soderquist B, Kahl BC, Denis O, Rwayane K, Corvec S, Francois P, Salipante F, Pantel A, Dunyach-Remy C, Laurent F, Lavigne JP; European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Staphylococci and Staphylococcal Diseases (ESGS). Staphylococcus pettenkoferi: an underrecognized species with clinically relevant antimicrobial resistance. A comprehensive genomic European study. Emerg Microbes Infect. 2026 Dec;15(1):2724635. doi: 10.1080/22221751.2026.2724635. Epub 2026 Sep 16.
- Magnan C, Plumet L, Morsli M, Dunyach-Remy C, Pouget C, Sotto A, Molle V, Lavigne J-P. A narrative review of coagulase-negative staphylococci in diabetic foot infections. Clin Microbiol Rev. 2025 Dec 11;38(4):e0012125. doi: 10.1128/cmr.00121-25. Epub 2025 Nov 4.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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