RT Journal Article
SR Electronic
T1 Decoration of the enterococcal polysaccharide antigen EPA is essential for virulence, cell surface charge and resistance to innate immunity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 479022
DO 10.1101/479022
A1 Robert E. Smith
A1 Bartłomiej Salamaga
A1 Piotr Szkuta
A1 Natalia Hajdamowicz
A1 Tomasz K. Prajsnar
A1 Gregory Bulmer
A1 Thierry Fontaine
A1 Justyna Kołodziejczyk
A1 Jean-Marie Herry
A1 Andrea Hounslow
A1 Mike P. Williamson
A1 Pascale Serror
A1 Stéphane Mesnage
YR 2018
UL http://biorxiv.org/content/early/2018/12/06/479022.abstract
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.