Enterococcus faecium produces membrane vesicles containing virulence factors and antimicrobial resistance related proteins

Abstract

<i>Enterococcus faecium</i> 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 <i>E. faecium</i> strains produce MVs. It presents a morphological as well as a proteomic analysis of MVs isolated from four different, clinically relevant <i>E. faecium</i> 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 <i>E. faecium</i> MVs may be utilized by the bacterium to release proteins promoting virulence, pathogenicity and antimicrobial resistance.<br><br>

<i>Significance -</i> Enterococcal infections, especially bacteremia and endocarditis, are challenging to treat because <i>E. faecium</i> 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 <i>E. faecium</i> strains representing four clinically relevant sequence types (STs), namely ST17, ST18, ST78, and ST192. The presented data suggest that <i>E. faecium</i> MVs are involved in virulence and antimicrobial resistance.