Biosynthesis and IroC-dependent export of the siderophore salmochelin are essential for virulence of Salmonella enterica serovar Typhimurium

Biosynthesis and IroC-dependent export of the siderophore salmochelin are essential for virulence of Salmonella enterica serovar Typhimurium
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DOI:
10.1111/j.1365-2958.2007.06089.x
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发表时间:
2008-03-01
影响因子:
3.6
通讯作者:
Fang, Ferric C.
Fang, Ferric C.
中科院分区:
生物学2区
文献类型:
--
作者:
Crouch, Marie-Laure V.;Castor, Margaret;Fang, Ferric C.

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在铁缺乏的情况下,鼠伤寒沙门氏菌会分泌两种儿茶酚型铁载体,即肠杆菌素及其糖基化衍生物沙门菌素。尽管负责肠杆菌素合成和获取的系统已得到充分表征,但沙门菌素的分泌和获取机制以及它在沙门氏菌致病性中的作用尚未完全了解。在此,我们通过对野生型和同基因突变细菌菌株的培养上清液进行液相色谱 - 质谱分析表明,主要易化子超家族泵EntS是肠杆菌素的主要输出蛋白,而ABC转运蛋白IroC可输出沙门菌素和肠杆菌素。生长促进实验表明,IroC并非如先前所述的那样是利用铁 - 肠杆菌素或铁 - 沙门菌素所必需的,但ABC转运蛋白FepD是利用这两种铁载体所必需的。缺乏沙门菌素合成或分泌的沙门氏菌突变体在小鼠全身性感染期间表现出致病性降低。
In response to iron deprivation, Salmonella enterica serovar Typhimurium secretes two catecholate-type siderophores, enterobactin and its glucosylated derivative salmochelin. Although the systems responsible for enterobactin synthesis and acquisition are well characterized, the mechanisms of salmochelin secretion and acquisition, as well as its role in Salmonella virulence, are incompletely understood. Herein we show by liquid chromatography-mass spectrometry analysis of culture supernatants from wild type and isogenic mutant bacterial strains that the Major Facilitator Superfamily pump EntS is the major exporter of enterobactin and the ABC transporter IroC exports both salmochelin and enterobactin. Growth promotion experiments demonstrate that IroC is not required for utilization of Fe-enterobactin or Fe-salmochelin, as had been previously suggested, but the ABC transporter protein FepD is required for utilization of both siderophores. Salmonella mutants deficient in salmochelin synthesis or secretion exhibit reduced virulence during systemic infection of mice.