Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA; Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
Curr Opin Biotechnol. 2021 Apr;68:213-220. doi: 10.1016/j.copbio.2021.01.012. Epub 2021 Jan 30.
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.
新抗生素候选药物的减少加上抗生素耐药性的增加，需要开发替代的抗菌药物。噬菌体编码的内溶素（lysins）是一类肽聚糖水解酶，被提议填补这一抗菌空白。过去 20 年，对内溶素的发现、结构/功能、工程、免疫原性、毒性/安全性以及在动物模型中的疗效的研究急剧增加。这些共同的努力导致了目前至少有三种不同的针对葡萄球菌属的内溶素的人体临床试验，这些内溶素对葡萄球菌属具有抗菌作用。可以预期，针对链球菌属的内溶素可能是下一个转化开发的目标。值得注意的是，链球菌病主要表现为可触及的粘膜，这对内溶素蛋白治疗应该是有益的。此外，在人和动物中，有许多已明确鉴定的链球菌病与单一物种有关，这进一步有利于靶向内溶素治疗。
