A Novel Truncated CHAP Modular Endolysin, CHAPSAP26-161, SAP26-161, That Lyses Staphylococcus aureus, , Acinetobacter baumannii, , and Clostridioides difficile, , and Exhibits Therapeutic Effects in a Mouse Model of A. baumannii Infection

초록

Development of novel antibacterial agents is imperative due to the increasing threat of antibiotic- resistant pathogens. This study aimed to develop the enhanced antibacterial activity and in- vivo efficacy of a novel truncated endolysin, CHAPSAP26-161, SAP26-161, derived from the endolysin LysSAP26, against multidrug-resistant bacteria. CHAPSAP26-161 SAP26-161 exhibited higher protein purification efficiency in E. coli and antibacterial activity than LysSAP26. Moreover, CHAPSAP26-161 SAP26-161 showed the higher lytic activity against A. baumannii with minimal bactericidal concentrations (MBCs) of 5-10 mu g/ml, followed by Staphylococcus aureus with MBCs of 10-25 mu g/ml. Interestingly, CHAPSAP26-161 SAP26-161 could lyse anaerobic bacteria, such as Clostridioides difficile, , with MBCs of 25-50 mu g/ml. At pH 4-8 and temperatures of 4oC-45oC, o C-45 o C, CHAPSAP26-161 SAP26-161 maintained antibacterial activity without remarkable difference. The lytic activity of CHAPSAP26-161 SAP26-161 was increased with Zn2+. 2+ . In vivo tests demonstrated the therapeutic effects of CHAPSAP26-161 SAP26-161 in murine systemicA. A. baumannii infection model. In conclusion, CHAPSAP26-161, SAP26-161, a truncated endolysin that retains only the CHAP domain from LysSAP26, demonstrated enhanced protein purification efficiency and antibacterial activity compared to LysSAP26. It further displayed broad-spectrum antibacterial effects against S. aureus, , A. baumannii, , and C. difficile. . Our in vitro and in-vivo results of CHAPSAP26-161 SAP26-161 highlights its promise as an innovative therapeutic option against those bacteria with multiple antibiotic resistance.

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