TsrA Regulates Virulence and Intestinal Colonization in Vibrio cholerae.
TsrA Regulates Virulence and Intestinal Colonization in Vibrio cholerae.
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TsrA调节霍乱弧菌的毒力和肠道定植。
DOI：
10.1128/msphere.01014-20
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发表时间：
2020-12-09
期刊：
影响因子：
4.8
通讯作者：
Davies BW
中科院分区：
文献类型：
--
作者：
DuPai CD;Cunningham AL;Conrado AR;Wilke CO;Davies BW
霍乱是一种潜在的致命疾病，在许多发展中国家流行。霍乱弧菌，这种疾病的潜在细菌，利用水平获得的遗传物质上编码的蛋白质感染人类。在这里，我们提供的证据表明，TsrA，弧菌科特异性蛋白质，在调节这些遗传因素中起着关键作用，是必不可少的霍乱弧菌在小鼠肠道模型中的毒力。霍乱弧菌的致病性菌株需要仔细调节水平获得的毒力因子，这些毒力因子主要位于水平获得的基因组岛（HAI）上。虽然已知TsrA是弧菌科特异性蛋白质，可调节关键的HAI毒力基因toxT和ctxA，但其在整个基因组中的更广泛功能尚不清楚。在这里，我们发现，删除tsrA的结果在基因组范围内的表达模式，在删除hns，一个广泛保守的细菌蛋白质，调节霍乱弧菌毒力的高度相关。这种相关性对于HAI上的基因座特别强，其中ΔtsrA突变体中所有差异表达的基因座也在Δhns突变体中差异表达。TsrA和H-NS功能之间的相关性延伸到体内毒力表型，其中tsrA的缺失补偿了霍乱弧菌中ToxR活性的丧失，并促进了小鼠肠道定殖的野生型水平。总而言之，我们发现TsrA通过抑制H-NS调节子中的关键HAI毒力基因和许多其他靶标来广泛控制霍乱弧菌的感染性。重要性霍乱是一种潜在的致命疾病，在许多发展中国家流行。霍乱弧菌，这种疾病的潜在细菌，利用水平获得的遗传物质上编码的蛋白质感染人类。在这里，我们提供的证据表明，TsrA，弧菌科特异性蛋白质，在调节这些遗传因素中起着关键作用，是必不可少的霍乱弧菌在小鼠肠道模型中的毒力。
Cholera is a potentially lethal disease that is endemic in much of the developing world. Vibrio cholerae, the bacterium underlying the disease, infects humans utilizing proteins encoded on horizontally acquired genetic material. Here, we provide evidence that TsrA, a Vibrionaceae-specific protein, plays a critical role in regulating these genetic elements and is essential for V. cholerae virulence in a mouse intestinal model. Pathogenic strains of Vibrio cholerae require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a Vibrionaceae-specific protein, is known to regulate the critical HAI virulence genes toxT and ctxA, its broader function throughout the genome is unknown. Here, we find that deletion of tsrA results in genomewide expression patterns that heavily correlate with those seen upon deletion of hns, a widely conserved bacterial protein that regulates V. cholerae virulence. This correlation is particularly strong for loci on HAIs, where all differentially expressed loci in the ΔtsrA mutant are also differentially expressed in the Δhns mutant. Correlation between TsrA and H-NS function extends to in vivo virulence phenotypes where deletion of tsrA compensates for the loss of ToxR activity in V. cholerae and promotes wild-type levels of mouse intestinal colonization. All in all, we find that TsrA broadly controls V. cholerae infectivity via repression of key HAI virulence genes and many other targets in the H-NS regulon. IMPORTANCE Cholera is a potentially lethal disease that is endemic in much of the developing world. Vibrio cholerae, the bacterium underlying the disease, infects humans utilizing proteins encoded on horizontally acquired genetic material. Here, we provide evidence that TsrA, a Vibrionaceae-specific protein, plays a critical role in regulating these genetic elements and is essential for V. cholerae virulence in a mouse intestinal model.