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Effects of Pyrogallol on Growth and Cytotoxicity of Wild-Type and katG Mutant Strains of Vibrio vulnificus

机译:邻苯三酚对创伤弧菌野生型和katG突变株生长和细胞毒性的影响

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摘要

Vibrio vulnificus is a causative agent of fatal septicemia and necrotic wound infection and the pathogen infection became an important public health problem in many counties. Vibrio vulnificus causes RtxA1 toxin-induced acute cell death. We tried to identify natural products that inhibit the acute cytotoxicity of V. vulnificus using a lactate hydrogenase assay. A polyphenol pyrogallol protected HeLa cells from V. vulnificus-induced cytotoxicity. Pyrogallol also decreased the growth of V. vulnificus; this inhibitory effect was more significant during log phase than stationary phase. To further elucidate the inhibitory mechanism, pyrogallol-induced toxicity was compared between a V. vulnificus catalase-peroxidase mutant (katG) and the isogenic wild-type MO6-24/O strains. No growth was observed for the katG mutant in the presence of pyrogallol (50 μg/mL) even after 24 h, whereas the wild-type strain demonstrated growth recovery following a prolonged lag phase. Pyrogallol-mediated growth inhibition of the katG mutant strain was partially rescued by exogenous catalase treatment. These results indicate that the mechanism by which pyrogallol inhibits the growth and cytotoxicity of V. vulnificus likely involves polyphenol-induced prooxidant damage. Taken together, these results suggest that pyrogallol has potential for development as a new paradigm drug to treat infectious diseases.
机译:创伤弧菌是致命败血病和坏死性伤口感染的病原体,病原体感染已成为许多县的重要公共卫生问题。创伤弧菌引起RtxA1毒素诱导的急性细胞死亡。我们试图使用乳酸加氢酶测定法鉴定抑制V. vulnificus急性细胞毒性的天然产物。多酚邻苯三酚可以保护HeLa细胞免受V. vulnificus诱导的细胞毒性作用。邻苯三酚还减少了V. vulnificus的生长。这种抑制作用在对数期比固定期更显着。为了进一步阐明其抑制机理,在V. vulnificus过氧化氢酶过氧化物酶突变体(katG -)和同基因野生型MO6-24 / O菌株之间比较了邻苯三酚诱导的毒性。在连苯三酚(50μg/ mL)存在下,即使在24 h后,katG -突变体也未观察到生长,而野生型菌株在延长的滞后阶段后显示出生长恢复。通过外源过氧化氢酶处理部分挽救了间苯三酚介导的katG -突变株的生长抑制。这些结果表明,邻苯三酚可抑制 V 的生长和细胞毒性。 vulnificus 可能涉及多酚引起的促氧化剂损伤。综上所述,这些结果表明,邻苯三酚具有开发作为治疗传染病的新范例药物的潜力。

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