A Novel Truncated CHAP Modular Endolysin, CHAP SAP26 -161, That Lyses Staphylococcus aureus , Acinetobacter baumannii , and Clostridioides difficile , and Exhibits Therapeutic Effects in a Mouse Model of A. baumannii Infection
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Development of novel antibacterial agents is imperative due to the increasing threat of antibioticresistant pathogens. This study aimed to develop the enhanced antibacterial activity and in-vivo efficacy of a novel truncated endolysin, CHAPSAP26-161, derived from the endolysin LysSAP26, against multidrug-resistant bacteria. CHAPSAP26-161 exhibited higher protein purification efficiency in E. coli and antibacterial activity than LysSAP26. Moreover, CHAPSAP26-161 showed the higher lytic activity against A. baumannii with minimal bactericidal concentrations (MBCs) of 5–10 μg/ml, followed by Staphylococcus aureus with MBCs of 10–25 μg/ml. Interestingly, CHAPSAP26-161 could lyse anaerobic bacteria, such as Clostridioides difficile, with MBCs of 25–50 μg/ml. At pH 4–8 and temperatures of 4o C–45o C, CHAPSAP26-161 maintained antibacterial activity without remarkable difference. The lytic activity of CHAPSAP26-161 was increased with Zn2+. In vivo tests demonstrated the therapeutic effects of CHAPSAP26-161 in murine systemic A. baumannii infection model. In conclusion, CHAPSAP26-161, 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 highlights its promise as an innovative therapeutic option against those bacteria with multiple antibiotic resistance.
Abstract
Development of novel antibacterial agents is imperative due to the increasing threat of antibioticresistant pathogens. This study aimed to develop the enhanced antibacterial activity and in-vivo efficacy of a novel truncated endolysin, CHAPSAP26-161, derived from the endolysin LysSAP26, against multidrug-resistant bacteria. CHAPSAP26-161 exhibited higher protein purification efficiency in E. coli and antibacterial activity than LysSAP26. Moreover, CHAPSAP26-161 showed the higher lytic activity against A. baumannii with minimal bactericidal concentrations (MBCs) of 5–10 μg/ml, followed by Staphylococcus aureus with MBCs of 10–25 μg/ml. Interestingly, CHAPSAP26-161 could lyse anaerobic bacteria, such as Clostridioides difficile, with MBCs of 25–50 μg/ml. At pH 4–8 and temperatures of 4o C–45o C, CHAPSAP26-161 maintained antibacterial activity without remarkable difference. The lytic activity of CHAPSAP26-161 was increased with Zn2+. In vivo tests demonstrated the therapeutic effects of CHAPSAP26-161 in murine systemic A. baumannii infection model. In conclusion, CHAPSAP26-161, 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 highlights its promise as an innovative therapeutic option against those bacteria with multiple antibiotic resistance.
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