Antibacterial action, proteolytic immunity, and in vivo activity of a Vibrio cholerae microcin,Cell Host & Microbe

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Antibacterial action, proteolytic immunity, and in vivo activity of a Vibrio cholerae microcin
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-09-10 , DOI: 10.1016/j.chom.2024.08.012
Sun-Young Kim ₁ , Justin R Randall ₁ , Richard Gu ₁ , Quoc D Nguyen ₁ , Bryan W Davies ₂

Affiliation

Microcins are small antibacterial proteins that mediate interbacterial competition. Their narrow-spectrum activity provides opportunities to discover microbiome-sparing treatments. However, microcins have been found almost exclusively in Enterobacteriaceae. Their broader existence and potential implications in other pathogens remain unclear. Here, we identify and characterize a microcin active against pathogenic Vibrio cholerae: MvcC. We show that MvcC is reliant on the outer membrane porin OmpT to cross the outer membrane. MvcC then binds the periplasmic protein OppA to reach and disrupt the cytoplasmic membrane. We demonstrate that MvcC’s cognate immunity protein is a protease, which precisely cleaves MvcC to neutralize its activity. Importantly, we show that MvcC is active against diverse cholera isolates and in a mouse model of V. cholerae colonization. Our results provide a detailed analysis of a microcin outside of Enterobacteriaceae and its potential to influence V. cholerae infection.

中文翻译：

抗菌作用、蛋白水解免疫和霍乱弧菌微霉素的体内活性

Microcin 是介导细菌间竞争的小抗菌蛋白。它们的窄谱活性为发现保留微生物组的治疗方法提供了机会。然而，微霉素几乎只存在于肠杆菌科中。它们在其他病原体中的更广泛存在和潜在影响仍不清楚。在这里，我们鉴定并表征了一种对致病性霍乱弧菌具有活性的微霉素：MvcC。我们表明 MvcC 依赖于外膜孔蛋白 OmpT 穿过外膜。然后 MvcC 结合周质蛋白 OppA 以到达并破坏细胞质膜。我们证明 MvcC 的同源免疫蛋白是一种蛋白酶，可精确裂解 MvcC 以中和其活性。重要的是，我们表明 MvcC 对多种霍乱分离株和霍乱弧菌 定植的小鼠模型具有活性。我们的结果详细分析了肠杆菌科以外的微霉素及其影响霍乱弧菌 感染的可能性。

更新日期：2024-09-10

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