Enterococcus faecalisbacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence ofCandida albicans

Abstract

Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species also are among the most important and problematic, opportunistic nosocomial pathogens. Surprisingly, these two species antagonize each other's virulence in both nematode infection and in vitro biofilm models. We report here the identification of the E. faecalis bacteriocin, EntV, produced from the entV (ef1097) locus, as both necessary and sufficient for the reduction of C. albicans virulence and biofilm formation through the inhibition of hyphal formation, a critical virulence trait. A synthetic version of the mature 68-aa peptide potently blocks biofilm development on solid substrates in multiple media conditions and disrupts preformed biofilms, which are resistant to current antifungal agents. EntV 68 is protective in three fungal infection models at nanomolar or lower concentrations. First, nematodes treated with the peptide at 0.1 nM are completely resistant to killing by C. albicans. The peptide also protects macrophages and augments their antifungal activity. Finally, EntV 68 reduces epithelial invasion, inflammation, and fungal burden in a murine model of oropharyngeal candidiasis. In all three models, the peptide greatly reduces the number of fungal cells present in the hyphal form. Despite these profound effects, EntV 68 has no effect on C. albicans viability, even in the presence of significant host-mimicking stresses. These findings demonstrate that EntV has potential as an antifungal agent that targets virulence rather than viability.Candida albicans | Enterococcus faecalis | biofilms | bacteriocins

Candida biofilm production is associated with higher mortality in patients with candidaemia

“…37 Furthermore, Graham et al (2017) demonstrated that a bacteriocin of Enterococcus faecalis potently inhibits hyphal growth. 38 In conclusion, our analysis confirmed that the ability to form biofilms especially with intermediate/high metabolic activity is related to higher mortality in candidaemia. Furthermore, it highlights that considering biofilm mass and metabolic activity equivalent may lead…”

“…Morales et al (2013) showed that phenazines derived from P aeruginosa impair C albicans metabolic activity and influence the cellular morphology, cell‐cell interactions and biofilm formation . Furthermore, Graham et al (2017) demonstrated that a bacteriocin of Enterococcus faecalis potently inhibits hyphal growth …”

Development and regulation of single- and multi-species Candida albicans biofilms

“…4d). Similarly, Enterococcus faecalis secretes the bacteriocin EntV, which inhibits C. albicans hyphal and biofilm formation and disrupts mature C. albicans bio-films 142 . Finally, the LuxS quorum sensing system in S. gordonii is needed for the increase in biomass observed when S. gordonii and C. albicans form a dual-species bio-film 125 .…”

Disinfection of Infected Root Canals: Nanosilver Has Good Potential

“…Microbial biofilms account for more than 80% of microbial infections in the body. E. faecalis also colonizes the root canal and the apex surface in the form of a biofilm . Therefore, the E. faecalis biofilm is the object that root canal disinfectant needs to remove .…”