PT  - JOURNAL ARTICLE
AU  - Robert E. Smith
AU  - Bartłomiej Salamaga
AU  - Piotr Szkuta
AU  - Natalia Hajdamowicz
AU  - Tomasz K. Prajsnar
AU  - Gregory Bulmer
AU  - Thierry Fontaine
AU  - Justyna Kołodziejczyk
AU  - Jean-Marie Herry
AU  - Andrea Hounslow
AU  - Mike P. Williamson
AU  - Pascale Serror
AU  - Stéphane Mesnage
TI  - Decoration of the enterococcal polysaccharide antigen EPA is essential for virulence, cell surface charge and resistance to innate immunity
AID  - 10.1101/479022
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 479022
4099  - http://biorxiv.org/content/early/2018/12/06/479022.short
4100  - http://biorxiv.org/content/early/2018/12/06/479022.full
AB  - Enterococcus faecalis is an opportunistic pathogen with an intrinsically high resistance to lysozyme, a key effector of the innate immune system. This high level of resistance requires several genes (oatA, pgdA, dltA and sigV) acting synergistically to inhibit both the enzymatic and cationic antimicrobial peptide activities of lysozyme. We sought to identify novel genes modulating E. faecalis resistance to lysozyme. Random transposon mutagenesis carried out in the quadruple oatA/pgdA/dltA/sigV mutant led to the identification of several independent insertions clustered on the chromosome. These mutations were located in a locus referred to as the enterococcal polysaccharide antigen (EPA) variable region located downstream of the highly conserved epaA-epaR genes proposed to encode a core synthetic machinery. The epa variable region was previously proposed to be responsible for EPA decorations, but the role of this locus remains largely unknown. Here, we show that EPA decoration contributes to resistance towards charged antimicrobials and underpins virulence in the zebrafish model of infection by conferring resistance to phagocytosis. Collectively, our results indicate that the production of the EPA rhamnopolysaccharide backbone is not sufficient to promote E. faecalis infections and reveal an essential role of the modification of this surface polymer for enterococcal pathogenesis.