Cell Wall-anchored Proteins of Enterococcus faecium: Exploring a Novel Surface

Abstract

The past 4 years my research focussed on the identification, expression and function of surface-exposed LPXTG proteins and filamentous structures (also called pili or fimbriae) at the Enterococcus faecium cell wall. E. faecium is a commensal organism of the mammalian gastrointestinal tract, but the last two decades it has been recognized as an nosocomial pathogen causing wound infections, bacteremia, and endocarditis. Hospital-aqcuired (HA-) E. faecium isolates recovered from sites of infection and responsible for nosocomial outbreaks are multi-antibiotic resistant and therefore difficult to treat. The results I have obtained showed that the clinically relevant hospital-acquired E. faecium isolates were specifically enriched in five LPXTG surface proteins (Orf903, Orf904.5, Orf906.7, EcbA and SgrA) when compared to clinically non-relevant non-HA-E. faecium isolates. Both EcbA and SgrA LPXTG surface proteins were functionally characterized, and EcbA showed binding to collagen type V and SgrA to nidogen-2. The collagen type V and nidogen-2 molecules are components of the extracellular matrix, an entry site for pathogenic bacteria into the host. Furthermore, I was the first to identify the presence of surface-exposed pili in E. faecium. The genes of two of the four pilin gene clusters present in E. faecium TX0016 encoded two distinct types of surface-exposed pili, designated PilA and PilB. These pili were only expressed at 37C and not at 21C, suggesting that pili are specifically produced in a mammalian host, but not in the environment. The two surface proteins and expression of pili may provide HA-E. faecium with a selective advantage in the hospital setting and are potential targets for novel vaccines to combat nosocomial E. faecium infections.