Engineering of lysin by fusion of antimicrobial peptide (cecropin A) enhances its antibacterial properties against multidrug-resistant Acinetobacter baumannii

• DOI: 10.3389/fmicb.2022.988522
• Publication Date: 2022-09-26T08:58:20Z
• Authors: Md Maidul Islam; Dooyoung Kim; Kyeongmin Kim; Su-Jin Park; Samia Akter; Jeongah Kim; Seunghyeok Bang; Shukho Kim; Jungmin Kim; Je Chul Lee; Chang-Won Hong; Minsang Shin
• Keywords: Lysin; Acinetobacter baumannii

Most clinical isolates of Acinetobacter baumannii , a nosocomial pathogen, are multidrug-resistant (MDR), fueling the search for alternative therapies. Bacteriophage-derived endolysins have potent antibacterial activities and considered as alternatives to antibiotics against A. infection. Gram-negative bacteria possess outer lipid membrane that prevents direct contact between cell wall. We hypothesized fusion antimicrobial peptide (AMP) with endolysin could help reduce bacterial resistance increase activity by permeability action. Accordingly, we fused cecropin A, commonly used AMP, N-terminus AbEndolysin, which enhances bactericidal chimeric endolysin. The A-fused AbEndolysin increased at least 2–8 fold various MDR isolates. in vitro results also showed higher lysis than parental lysin. engineered (eAbEndolysin) synergistic effects beta-lactam cefotaxime, ceftazidime, aztreonam, an additive effect meropenem imipenem. eAbEndolysin had no cytotoxic on A549 line rescued mice (40% survival rate) from systemic Together, these findings suggest potential lysin therapy may prompt its use antibiotics.