Enterococcus infection biology: lessons from invertebrate host models

Abstract

The enterococci are commensals of the gastrointestinal tract of many metazoans, from insects to humans. While they normally do not cause disease in the intestine, they can become pathogenic when they infect sites outside of the gut. Recently, the enterococci have become important nosocomial pathogens, with the majority of human enterococcal infections caused by two species, Enterococcus faecalis and Enterococcus faecium. Studies using invertebrate infection models have revealed insights into the biology of enterococcal infections, as well as general principles underlying host innate immune defense. This review highlights recent findings on Enterococcus infection biology from two invertebrate infection models, the greater wax moth Galleria mellonella and the free-living bacteriovorous nematode Caenorhabditis elegans.

Figure 1

Key features of two invertebrate models

Figure 2. Mechanisms of enterococcal virulence

A. Enterococci produce a number of enzymes (e.g., hyaluronidase, gelatinase, and serine proteases) that degrade the host extracellular matrix, which allow the bacteria to invade host tissues. B. E. faecalis expresses several adhesins that allow it to bind the extracellular matrix and cell surface of the host. Aggregation substance (AS) facilitates the adherence of E. faecalis to extracellular matrix proteins. Ace and Fss are bacterial adhesins that bind collagen and fibrin, respectively. C. Cross-sections of C. elegans animals showing the intestinal lumen. After infection with E. faecalis, the C. elegans gut becomes distended with live enterococcal cells, forming a persistent infection in the worm (left). Most enterococcal cells are intact, with some even undergoing fission. In contrast, nearly all E. coli are degraded by the C. elegans pharyngeal grinder and intestine (right). Microvilli (mv) and intestinal epithelial cell (IEC) are labeled. D. Enterococcal gelatinase GelE aids in evading the immune system of both G. mellonella and humans. GelE degrades cecropin, an insect antimicrobial peptide that is induced early in infection. Additionally, GelE is able to hydrolyze human C3a and degrade C3b, two complement proteins generated by C3 activation. This inhibits opsonization, as well as the formation of the membrane attack complex, two important roles of the complement cascade.