Secretion, but not overall synthesis, of catecholate siderophores contributes to virulence of extraintestinal pathogenic Escherichia coli
Secretion, but not overall synthesis, of catecholate siderophores contributes to virulence of extraintestinal pathogenic Escherichia coli
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DOI：
10.1111/j.1365-2958.2011.07570.x
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发表时间：
2011-04-01
影响因子：
3.6
通讯作者：
Dozois, Charles M.
中科院分区：
文献类型：
--
作者：
Caza, Melissa;Lepine, Francois;Dozois, Charles M.
肠道外致病性大肠杆菌（ExPEC）在感染过程中利用铁载体摄取铁。肠杆菌素和沙门菌素是一些ExPEC菌株和其他致病性肠杆菌产生的儿茶酚盐类铁载体。在家禽ExPEC菌株chi7122的铁载体输出和合成突变体在鸡感染模型中进行了测试。在单一菌株感染中，铁载体阴性（ΔentD Δiuc）、ΔentS和ΔentS ΔiroC输出突变体在组织和血液中致病性减弱，而ΔiroC输出突变体仅在血液中致病性减弱。有趣的是，仅产生气杆菌素的ΔentD突变体保持完全的毒力，并且在ΔentS ΔiroC突变体中entD的缺失恢复了毒力。对输出突变体中铁载体的液相色谱 - 串联质谱（LC - MS/MS）定量分析表明，entS的缺失会损害肠杆菌素和单葡萄糖基化肠杆菌素的分泌，而iroC的缺失会损害二 - 和三 - 葡萄糖基化肠杆菌素的分泌。entS和/或iroC的缺失导致铁载体单体在细胞内积累以及分泌增加。儿茶酚盐类铁载体输出突变体在混合感染模型中也表现出适应性降低。相比之下，儿茶酚盐类铁载体合成突变体（ΔentD和ΔiroB）与野生型菌株竞争能力相同。结果表明，EntS和IroC介导儿茶酚盐类铁载体的特定输出，并且这些输出蛋白对ExPEC毒力的作用取决于肠杆菌素的合成，当其他铁载体如气杆菌素起作用时，肠杆菌素的合成并非必需。
P>Extraintestinal pathogenic Escherichia coli (ExPEC) use siderophores to sequester iron during infection. Enterobactin and salmochelins are catecholate siderophores produced by some ExPEC strains and other pathogenic enterobacteria. Siderophore export and synthesis mutants of avian ExPEC strain chi 7122 were tested in a chicken infection model. In single-strain infections, siderophore-negative (Delta entD Delta iuc), Delta entS and Delta entS Delta iroC export mutants were attenuated in tissues and blood, whereas the Delta iroC export mutant was only attenuated in blood. Interestingly, the Delta entD mutant, producing only aerobactin, retained full virulence, and loss of entD in the Delta entS Delta iroC mutant restored virulence. LC-MS/MS quantification of siderophores in export mutants demonstrated that loss of entS impaired enterobactin and mono-glucosylated enterobactin secretion, whereas loss of iroC impaired di- and tri-glucosylated enterobactin secretion. Loss of entS and/or iroC resulted in intracellular accumulation and increased secretion of siderophore monomers. Catecholate siderophore export mutants also demonstrated decreased fitness in a co-challenge infection model. By contrast, catecholate siderophore synthesis mutants (Delta entD and Delta iroB) competed as well as the wild-type strain. Results establish that EntS and IroC mediate specific export of catecholate siderophores and the role of these exporters for ExPEC virulence is contingent on enterobactin synthesis, which is not required when other siderophores like aerobactin are functional.