Engineered Hybrid Lantibiotic that Selectively Combats Infections Caused by Staphylococcus aureus

• DOI: 10.1021/acsinfecdis.4c00541
• Publication Date: 2024-10-29T18:24:16Z
• Authors: Yongcheng He; Jiarong Deng; Xinyi Zhong; Shujun Dai; Xu Song; Yuanfeng Zou; Gang Ye; Xun Zhou; Zhongqiong Yin; Hongping Wan; Xinghong Zhao
• Keywords: Lantibiotics; Anti-Infective Agents

The rapid emergence of antibiotic-resistant strains Staphylococcus aureus presents a substantial challenge to global public health, underscoring the urgent need for novel antibiotics with diverse mechanisms action. In this study, we conducted mutagenesis on C-terminal region lantibiotic ripcin C enhance its antimicrobial efficacy against S. aureus. resulting optimized variant, CP23A, demonstrated potent and selective activity, minimal inhibitory concentration 2-4 mg/L Beyond strong properties, CP23A exhibited significant antibiofilm activity methicillin-resistant (MRSA). Mechanistic studies revealed that, in addition targeting lipid II, disrupts bacterial membranes, capability absent C, which may contribute superior effects. Moreover, displayed favorable biosafety plasma stability profiles. Notably, mouse model MRSA-induced mastitis, effectively reduced load, alleviated inflammation, preserved normal histomorphology mammary glands. This study introduces as promising antibiotic candidate treatment MRSA-related infections.