Enterococcus faecium produces membrane vesicles containing virulence factors and antimicrobial resistance related
T Wagner1, B Joshi1, J Janice2
1Research Group of Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of Norway, Norway.
Abstract:
Enterococcus faecium is a commensal but also a bacteremia causing pathogen, which is inherently resistant to several antimicrobials and has a great ability to acquire new traits. Bacterial membrane vesicles (MVs) are increasingly recognized as a mode of cell-free communication and a way to deliver virulence factors and/or antimicrobial resistance determinants. These features make MVs interesting research targets in research on critical hospital pathogens. This study describes for the first time that E. faecium strains produce MVs. It presents a morphological as well as a proteomic analysis of MVs isolated from four different, clinically relevant E. faecium strains grown under two different conditions and identifies MV-associated proteins in all of them. Interestingly, 11 virulence factors are found among the MV-associated proteins, including biofilm-promoting proteins and extracellular matrix-binding proteins, which may aid in enterococcal colonization. Additionally, 11 antimicrobial resistance-related proteins were MV-associated. Among those, all proteins encoded by the vanA-cluster of a vancomycin resistant strain were found to be MV-associated. This implies that E. faecium MVs may be utilized by the bacterium to release proteins promoting virulence, pathogenicity and antimicrobial resistance.
Significance:
Enterococcal infections, especially bacteremia and endocarditis, are challenging to treat because E. faecium have acquired resistance to multiple classes of antimicrobials, including ampicillin, aminoglycosides, and glycopeptides. Thus, research on different modes of enterococcal pathogenicity is warranted. This study utilized a proteomic approach to identify MV-associated proteins of different nosocomial E. faecium strains representing four clinically relevant sequence types (STs), namely ST17, ST18, ST78, and ST192. The presented data suggest that E. faecium MVs are involved in virulence and antimicrobial resistance.
Insights
This study reveals that Enterococcus faecium releases membrane vesicles (MVs) carrying virulence factors and antimicrobial resistance proteins. These MVs may contribute to E. faecium pathogenicity and treatment challenges.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Enterococcus faecium is a significant nosocomial pathogen causing infections like bacteremia and endocarditis.
- E. faecium exhibits inherent antimicrobial resistance and readily acquires new resistance traits, complicating treatment.
- Bacterial membrane vesicles (MVs) are emerging as key mediators of intercellular communication and virulence factor dissemination.
Purpose of the Study:
- To investigate the production and cargo of membrane vesicles (MVs) from clinically relevant Enterococcus faecium strains.
- To characterize the proteomic content of E. faecium MVs, focusing on virulence factors and antimicrobial resistance determinants.
- To explore the potential role of MVs in E. faecium pathogenicity and antimicrobial resistance.
Main Methods:
- Isolation and morphological analysis of MVs from four distinct E. faecium strains.
- Proteomic analysis to identify proteins associated with the isolated MVs.
- Comparative analysis of MV protein content under different growth conditions.
Main Results:
- Enterococcus faecium strains were confirmed to produce MVs.
- Proteomic analysis identified numerous MV-associated proteins, including 11 virulence factors and 11 antimicrobial resistance proteins.
- Notably, all proteins from the vanA-cluster of a vancomycin-resistant strain were found in its MVs.
- MV-associated virulence factors included biofilm-promoting and extracellular matrix-binding proteins.
Conclusions:
- E. faecium MVs play a significant role in disseminating virulence factors and antimicrobial resistance genes.
- These MVs contribute to E. faecium's colonization, pathogenicity, and resistance to antibiotics.
- Understanding MV function is crucial for developing novel therapeutic strategies against E. faecium infections.
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