Vibrio vulnificus is a halophilic estuarine bacterium causing severe opportunistic infections. To successfully establish an infection, V. vulnificus must adapt to redox fluctuations in vivo. In the present study, we show that deletion of V. vulnificus fexA gene caused hypersensitivity to acid and reactive oxygen species. The ΔfexA mutant exhibited severe in vivo survival defects. For deeper understanding the role of fexA gene on the successful V. vulnificus infection, we analyzed differentially expressed genes in ΔfexA mutant in comparison with wild type under aerobic, anaerobic or in vivo culture conditions by genome-scale DNA microarray analyses. Twenty-two genes were downregulated in the ΔfexA mutant under all three culture conditions. Among them, cydAB appeared to dominantly contribute to the defective phenotypes of the ΔfexA mutant. The fexA deletion induced compensatory point mutations in the cydAB promoter region over subcultures, suggesting essentiality. Those point mutations (PcydSMs) restored bacterial growth, motility, cytotoxicity ATP production and mouse lethality in the ΔfexA mutant. These results indicate that the cydAB operon, being regulated by FexA, plays a crucial role in V. vulnificus survival under redox-fluctuating in vivo conditions. The FexA-CydAB axis should serve an Achilles heel in the development of therapeutic regimens against V. vulnificus infection.

中文翻译：

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fexA调控的细胞色素d氧化酶复合物是创伤弧菌体内存活的致命弱点。


创伤弧菌是一种嗜盐河口细菌，可引起严重的机会性感染。为了成功建立感染，创伤弧菌必须适应体内氧化还原波动。在本研究中，我们发现创伤弧菌 fexA 基因的缺失会导致对酸和活性氧的过敏。 ΔfexA突变体表现出严重的体内生存缺陷。为了更深入地了解 fexA 基因对创伤弧菌成功感染的作用，我们通过基因组规模 DNA 微阵列分析，分析了 ΔfexA 突变体与野生型在有氧、厌氧或体内培养条件下的差异表达基因。在所有三种培养条件下，ΔfexA 突变体中有 22 个基因被下调。其中，cydAB 似乎主要导致 ΔfexA 突变体的缺陷表型。 fexA 缺失在亚培养物中诱导了 cydAB 启动子区域的补偿性点突变，这表明了其重要性。这些点突变 (PcydSM) 恢复了 ΔfexA 突变体中的细菌生长、运动性、细胞毒性 ATP 产生和小鼠致死率。这些结果表明，受 FexA 调节的 cydAB 操纵子对创伤弧菌在体内氧化还原波动条件下的存活起着至关重要的作用。 FexA-CydAB 轴应该成为开发针对创伤弧菌感染的治疗方案的致命弱点。