The Vibrio cholerae ToxR-regulated porin OmpU confers resistance to antimicrobial peptides
The Vibrio cholerae ToxR-regulated porin OmpU confers resistance to antimicrobial peptides
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DOI：
10.1128/iai.72.6.3577-3583.2004
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Waldor, MK
中科院分区：
文献类型：
--
作者：
Mathur, J;Waldor, MK
BPI（杀菌/通透性增加）是一种有效的抗菌蛋白，最近报道其作为表面蛋白在人胃肠道上皮细胞上表达。在这项研究中，我们调查了霍乱弧菌（一种引起霍乱的小肠病原体）对BPI衍生肽P2的抗性。与大肠杆菌和鼠伤寒沙门氏菌不同，霍乱弧菌对P2的耐药性不依赖于BipA GT3。相反，我们发现，霍乱弧菌致病性的主要调节因子ToxR通过调节外膜蛋白OmpU的产生来控制对P2的抗性。toxR和ompU突变体对P2的敏感性比野生型细胞高至少100倍。OmpU还赋予了对多粘菌素B硫酸盐的抗性，这表明该孔蛋白可能通过共同的机制赋予对阳离子抗菌蛋白的抗性。对静止期细胞的研究表明，ToxR抑制的孔蛋白OmpT也可能有助于P2抗性。最后，虽然孔蛋白介导的抗微生物肽的耐药性的机制仍然难以捉摸，我们的数据表明，OmpU缺陷的霍乱弧菌的BPI肽的敏感性是不是由于一个普遍缺陷的外膜。
BPI (bactericidal/permeability-increasing) is a potent antimicrobial protein that was recently reported to be expressed as a surface protein on human gastrointestinal tract epithelial cells. In this study, we investigated the resistance of Vibrio cholerae, a small-bowel pathogen that causes cholera, to a BPI-derived peptide, P2. Unlike in Escherichia coli and Salmonella enterica serovar Typhimurium, resistance to P2 in V. cholerae was not dependent on the BipA GTPase. Instead, we found that ToxR, the master regulator of V. cholerae pathogenicity, controlled resistance to P2 by regulating the production of the outer membrane protein OmpU. Both toxR and ompU mutants were at least 100-fold more sensitive to P2 than were wild-type cells. OmpU also conferred resistance to polymyxin B sulfate, suggesting that this porin may impart resistance to cationic antibacterial proteins via a common mechanism. Studies of stationary-phase cells revealed that the ToxR-repressed porin OmpT may also contribute to P2 resistance. Finally, although the mechanism of porin-mediated resistance to antimicrobial peptides remains elusive, our data suggest that the BPI peptide sensitivity of OmpU-deficient V. cholerae is not attributable to a generally defective outer membrane.