Evaluation of Pathogenicity Factors of Staphylococcus Pettenkoferi in Foot Wounds and Osteitis in Diabetic Patients
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Genetic diversity of Staphyloccocus pettenkoferi strains isolated from osteitis and non-diabetic wounds, blood cultures and nasal carriage.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Not applicable for this research on a ready-constituted collection of strains of Staphylococcus pettenkoferi
排除标准
- •Not applicable for this research on a ready-constituted collection of strains of Staphylococcus pettenkoferi
结局指标
主要结局
Genetic diversity of Staphyloccocus pettenkoferi strains isolated from osteitis and non-diabetic wounds, blood cultures and nasal carriage.
时间窗: 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).
次要结局
- Genetic diversity of Staphyloccocus pettenkoferi strains isolated from osteitis and non-diabetic wounds, blood cultures and nasal carriage.(3 - 6 months)
- Resistome in the strain population according to sample origin:osteitis(3 - 6 months)
- Resistome in the strain population according to sample origin: non-diabetic wounds(3 - 6 months)
- Resistome in the strain population according to sample origin: diabetic wounds(3 - 6 months)
- Resistome in the strain population according to sample origin: blood cultures(3 - 6 months)
- Resistome in the strain population according to sample origin: nasal carriage(3 - 6 months)
- Virulome in the strain population according to sample origin: osteitis(3 - 6 months)
- Virulome in the strain population according to sample origin: non-diabetic wounds(3 - 6 months)
- Virulome in the strain population according to sample origin: diabetic wounds(3 - 6 months)
- Virulome in the strain population according to sample origin: blood cultures(3 - 6 months)
- Virulome in the strain population according to sample origin: nasal carriage(3 - 6 months)
- Plasmids inthe strain population and according to sample origin: osteitis(3 - 6 months)
- Plasmids inthe strain population and according to sample origin: non-diabetic wounds(3 - 6 months)
- Plasmids inthe strain population and according to sample origin: diabetic wounds(3 - 6 months)
- Plasmids inthe strain population and according to sample origin: blood cultures(3 - 6 months)
- Plasmids inthe strain population and according to sample origin: nasal carriage(3 - 6 months)
- Phenotypic resistance profiles in the population in a subsample of 85 strains(6 - 14 months)
- Phenotypic resistance profiles in the population and according to sample origin: osteitis(6 - 14 months)
- Phenotypic resistance profiles in the population and according to sample origin: non-diabetic wounds(6 - 14 months)
- Phenotypic resistance profiles in the population and according to sample origin: diabetic wounds(6 - 14 months)
- Phenotypic resistance profiles in the population and according to sample origin: blood cultures(6 - 14 months)
- Phenotypic resistance profiles in the population and according to sample origin: nasal carriage(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(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(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(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(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(6 - 14 months)
- Bacterial growth rate according to sample origin in a sub-sample of 20 strains: osteitis(6 - 14 months)
- Bacterial growth rate according to sample origin in a sub-sample of 20 strains: non-diabetic wounds(6 - 14 months)
- Bacterial growth rate according to sample origin in a sub-sample of 20 strains: diabetic wounds(6 - 14 months)
- Bacterial growth rate according to sample origin in a sub-sample of 20 strains: blood cultures(6 - 14 months)
- Bacterial growth rate according to sample origin in a sub-sample of 20 strains: nasal carriage(6 - 14 months)
- Virulence profiles according to sample origin in a sub-sample of 3 strains: osteitis(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(6 - 14 months)
- Virulence profiles according to sample origin in a sub-sample of 3 strains: diabetic wounds(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(6 - 14 months)
- Virulence profiles according to sample origin in a sub-sample of 3 strains: blood cultures(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(6 - 14 months)
- Virulence profiles according to sample origin in a sub-sample of 3 strains: nasal carriage(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(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 non-diabetic wounds(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(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 osteitis(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(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(Up to 48 hours)