State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Institute of Microbiology and Epizootics, Centre for Infection Medicine, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
NPJ Biofilms Microbiomes. 2023 Apr 6;9(1):16. doi: 10.1038/s41522-023-00385-5.
Antibiotic resistance and the ability to form biofilms of Enterococcus faecalis have compromised the choice of therapeutic options, which triggered the search for new therapeutic strategies, such as the use of phage endolysins and antimicrobial peptides. However, few studies have addressed the synergistic relationship between these two promising options. Here, we investigated the combination of the phage endolysin Ply2660 and the antimicrobial peptide LL-37 to target drug-resistant biofilm-producing E. faecalis. In vitro bactericidal assays were used to demonstrate the efficacy of the Ply2660-LL-37 combination against E. faecalis. Larger reductions in viable cell counts were observed when Ply2660 and LL-37 were applied together than after individual treatment with either substance. Transmission electron microscopy revealed that the Ply2660-LL-37 combination could lead to severe cell lysis of E. faecalis. The mode of action of the Ply2660-LL-37 combination against E. faecalis was that Ply2660 degrades cell wall peptidoglycan, and subsequently, LL-37 destroys the cytoplasmic membrane. Furthermore, Ply2660 and LL-37 act synergistically to inhibit the biofilm formation of E. faecalis. The Ply2660-LL-37 combination also showed a synergistic effect for the treatment of established biofilm, as biofilm killing with this combination was superior to each substance alone. In a murine peritoneal septicemia model, the Ply2660-LL-37 combination distinctly suppressed the dissemination of E. faecalis isolates and attenuated organ injury, being more effective than each treatment alone. Altogether, our findings indicate that the combination of a phage endolysin and an antimicrobial peptide may be a potential antimicrobial strategy for combating E. faecalis.
肠球菌的抗生素耐药性和生物膜形成能力降低了治疗选择的多样性，这促使人们寻找新的治疗策略，如噬菌体裂解酶和抗菌肽的使用。然而，很少有研究涉及这两种有前途的选择之间的协同关系。在这里，我们研究了噬菌体裂解酶 Ply2660 和抗菌肽 LL-37 联合用于靶向耐药生物膜形成的粪肠球菌。体外杀菌实验用于证明 Ply2660-LL-37 联合对粪肠球菌的疗效。与单独使用任何一种物质相比，当 Ply2660 和 LL-37 一起使用时，活菌计数的减少更大。透射电子显微镜显示，Ply2660-LL-37 联合可导致粪肠球菌严重的细胞裂解。Ply2660-LL-37 联合对粪肠球菌的作用模式是 Ply2660 降解细胞壁肽聚糖，随后 LL-37 破坏细胞质膜。此外，Ply2660 和 LL-37 协同作用抑制粪肠球菌生物膜的形成。Ply2660-LL-37 联合对已建立的生物膜也表现出协同作用，因为这种联合处理的生物膜杀伤效果优于每种物质单独处理。在小鼠腹腔脓毒症模型中，Ply2660-LL-37 联合明显抑制粪肠球菌分离株的传播，并减轻器官损伤，比单独使用每种药物更有效。总之，我们的研究结果表明，噬菌体裂解酶和抗菌肽的联合使用可能是一种有潜力的抗粪肠球菌的抗菌策略。
