AUTHOR=Islam Md Maidul , Kim Dooyoung , Kim Kyeongmin , Park Su-Jin , Akter Samia , Kim Jeongah , Bang Seunghyeok , Kim Shukho , Kim Jungmin , Lee Je Chul , Hong Chang-Won , Shin Minsang 

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

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.988522

DOI=10.3389/fmicb.2022.988522

ISSN=1664-302X

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