Comparative transcriptomic analysis of Staphylococcus epidermidis associated with periprosthetic joint infection
Cody R Fisher1, Thao L Masters2, Stephen Johnson3
1Mayo Clinic Graduate School of Biomedical Sciences, Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA; Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
Staphylococcus epidermidis is part of the commensal microbiota of the skin and mucous membranes, though it can also act as a pathogen in certain scenarios, causing a range of infections, including periprosthetic joint infection (PJI). Transcriptomic profiling may provide insights into mechanisms by which S. epidermidis adapts while in a pathogenic compared to a commensal state. Here, a total RNA-sequencing approach was used to profile and compare the transcriptomes of 19 paired PJI-associated S. epidermidis samples from an in vivo clinical source and grown in in vitro laboratory culture. Genomic comparison of PJI-associated and publicly available commensal-state isolates were also compared. Of the 1919 total transcripts found, 145 were from differentially expressed genes (DEGs) when comparing in vivo or in vitro samples. Forty-two transcripts were upregulated and 103 downregulated in in vivo samples. Of note, metal sequestration-associated genes, specifically those related to staphylopine activity (cntA, cntK, cntL, and cntM), were upregulated in a subset of clinical in vivo compared to laboratory grown in vitro samples. About 70% of the total transcripts and almost 50% of the DEGs identified have not yet been annotated. There were no significant genomic differences between known commensal and PJI-associated S. epidermidis isolates, suggesting that differential genomics may not play a role in S. epidermidis pathogenicity. In conclusion, this study provides insights into phenotypic alterations employed by S epidermidis to adapt to infective and non-infected microenvironments, potentially informing future therapeutic targets for related infections.
Insights
Staphylococcus epidermidis adapts to infection by altering gene expression, not genomics. This study reveals phenotypic changes in pathogenic bacteria, offering potential therapeutic targets for infections like periprosthetic joint infection (PJI).
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Staphylococcus epidermidis is a common skin microbe that can cause serious infections, such as periprosthetic joint infection (PJI).
- Understanding how S. epidermidis transitions between commensal and pathogenic states is crucial for developing effective treatments.
Purpose of the Study:
- To compare the transcriptomes of S. epidermidis from in vivo (PJI) and in vitro (laboratory culture) conditions.
- To investigate genomic differences between pathogenic and commensal S. epidermidis isolates.
- To identify adaptive mechanisms and potential therapeutic targets for S. epidermidis infections.
Main Methods:
- Total RNA sequencing was used to profile and compare transcriptomes of 19 paired PJI-associated S. epidermidis samples (in vivo vs. in vitro).
- Genomic comparison of PJI-associated and publicly available commensal S. epidermidis isolates.
- Differential gene expression analysis was performed to identify significant changes.
Main Results:
- 145 differentially expressed genes (DEGs) were identified between in vivo and in vitro samples; 42 were upregulated and 103 downregulated in vivo.
- Metal sequestration genes (staphylopine activity) were upregulated in a subset of in vivo samples.
- No significant genomic differences were found between commensal and PJI-associated S. epidermidis, suggesting pathogenicity is not primarily driven by genomic variation.
Conclusions:
- S. epidermidis exhibits significant phenotypic alterations, particularly in gene expression, to adapt to different microenvironments (infective vs. non-infective).
- The study highlights the importance of phenotypic plasticity in bacterial adaptation and pathogenesis.
- Findings may inform the development of novel therapeutic strategies targeting S. epidermidis adaptation mechanisms.
