Application of bacteriophage-derived endolysins to combat streptococcal disease: current state and perspectives

The decline in new antibiotic candidates combined with an increase in antibiotic-resistance necessitates development of alternative antimicrobials. Bacteriophage-encoded endolysins (lysins) are a class of peptidoglycan hydrolases that have been proposed to fill this antimicrobial void. The past 20 years has seen a dramatic expansion of studies on endolysin discovery, structure/function, engineering, immunogenicity, toxicity/safety, and efficacy in animal models. These collective efforts have led to current human clinical trials on at least three different endolysins that are antimicrobial toward staphylococcal species. It can be anticipated that endolysins targeting streptococcal species may be next in line for translational development. Notably, streptococcal diseases largely manifest at accessible mucous membranes, which should be beneficial for protein therapeutics. Additionally, there are a number of well-identified streptococcal diseases in both humans and animals that are associated with a single species, further favoring a targeted endolysin therapeutic.