Enterococcus faecalis wound infections remain poorly understood. We demonstrate in vivo that E faecalis infection results in 2 different states: colonization or infection. We show that E faecalis infection modulates host immunity, resulting in persistent infection and delayed healing.

Enterococcus faecalis and Enterococcus faecium are common inhabitants of the human gastrointestinal tract, as well as frequent opportunistic pathogens. Enterococci cause a range of infections including, most frequently, infections of the urinary tract, catheterized urinary tract, bloodstream, wounds and surgical sites, and heart valves in endocarditis. Enterococcal infections are often biofilm-associated, polymicrobial in nature, and resistant to antibiotics of last resort. Understanding Enterococcal mechanisms of colonization and pathogenesis are important for identifying new ways to manage and intervene with these infections. We review vertebrate and invertebrate model systems applied to study the most common E. faecalis and E. faecium infections, with emphasis on recent findings examining Enterococcal-host interactions using these models. We discuss strengths and shortcomings of each model, propose future animal models not yet applied to study mono- and polymicrobial infections involving E. faecalis and E. faecium, and comment on the significance of anti-virulence strategies derived from a fundamental understanding of host-pathogen interactions in model systems.

Antibiotic-resistant infections are predicted to kill 10 million people worldwide per year by 2050 and to cost the global economy 100 trillion USD. Novel approaches and alternatives to conventional antibiotics are urgently required to combat antimicrobial resistance. We have synthesized a chitosan-based oligolysine antimicrobial peptide, CSM5-K5 (where CSM denotes chitosan monomer repeat units and K denotes lysine amino acid repeat units), that targets multidrug-resistant (MDR) bacterial species. Here, we show that CSM5-K5 exhibits rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA), MDR Escherichia coli, and vancomycin-resistant Enterococcus faecalis (VRE). Combinatorial therapy of CSM5-K5 with antibiotics to which each organism is otherwise resistant restores sensitivity to the conventional antibiotic. CSM5-K5 alone significantly reduced preformed bacterial biofilm by 2–4 orders of magnitude and, in combination with conventional antibiotics, reduced preformed biofilm by more than 2–3 orders of magnitude at subinhibitory concentrations. Moreover, using a mouse excisional wound infection model, CSM5-K5 treatment reduced bacterial burdens by 1–3 orders of magnitude and acted synergistically with oxacillin, vancomycin, and streptomycin to clear MRSA, VRE, and MDR E. coli, respectively. Importantly, little to no resistance against CSM5-K5 arose for any of the three MDR bacteria during 15 days of serial passage. Furthermore, low level resistance to CSM5-K5 that did arise for MRSA conferred increased susceptibility (collateral sensitivity) to the β-lactam antibiotic oxacillin. This work demonstrates the feasibility and benefits of using this synthetic cationic peptide as an alternative to, or in combination with, traditional antibiotics to treat infections caused by MDR bacteria.