Differential impact of lipopolysaccharide defects caused by loss of RfaH in Yersinia pseudotuberculosis and Yersinia pestis.

Differential impact of lipopolysaccharide defects caused by loss of RfaH in Yersinia pseudotuberculosis and Yersinia pestis.
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DOI:
10.1038/s41598-017-11334-6
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发表时间:
2017-09-07
期刊:
影响因子:
4.6
通讯作者:
Erickson DL
Erickson DL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hoffman JM;Sullivan S;Wu E;Wilson E;Erickson DL

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RfaH增强控制细菌表面特征如脂多糖(LPS)的一组选定操纵子的转录。以前的研究表明,rfaH可能是假结核耶尔森氏菌对抗菌趋化因子的耐药性和小鼠感染期间的存活所必需的。为了进一步研究RfaH在耶尔森氏菌LPS合成、对宿主防御肽的抗性以及致病性中的作用,我们构建了耶尔森氏菌ΔrfaH突变体。pseudotuberculosis IP 32953和Y.鼠疫KIM 6+。rfaH的损失影响LPS的合成在这两个物种,导致在较短的核心寡糖。在Y中rfaH的缺失增加了对多粘菌素和抗微生物趋化因子CCL 28的敏感性。假结核病而非Y.鼠疫在ΔrfaH突变体中,ddhD-wzz O-抗原基因簇中的基因(但不是核心寡糖基因)的转录降低。此外,特异性ddhD-wzz O-抗原簇基因被破坏的突变体产生的LPS与ΔrfaH突变体无法区分。这表明Y. pseudotuberculosis和Y.鼠疫杆菌产生具有以RfaH依赖性方式连接的单个O-抗原单元的寡糖核心。尽管增强了对宿主防御肽的敏感性,Y。pseudotuberculosis ΔrfaH株在小鼠体内没有减毒作用,表明rfaH不是急性感染所必需的。
RfaH enhances transcription of a select group of operons controlling bacterial surface features such as lipopolysaccharide (LPS). Previous studies have suggested that rfaH may be required for Yersinia pseudotuberculosis resistance to antimicrobial chemokines and survival during mouse infections. In order to further investigate the role of RfaH in LPS synthesis, resistance to host defense peptides, and virulence of Yersinia, we constructed ΔrfaH mutants of Y. pseudotuberculosis IP32953 and Y. pestis KIM6+. Loss of rfaH affected LPS synthesis in both species, resulting in a shorter core oligosaccharide. Susceptibility to polymyxin and the antimicrobial chemokine CCL28 was increased by loss of rfaH in Y. pseudotuberculosis but not in Y. pestis. Transcription of genes in the ddhD-wzz O-antigen gene cluster, but not core oligosaccharide genes, was reduced in ΔrfaH mutants. In addition, mutants with disruptions in specific ddhD-wzz O-antigen cluster genes produced LPS that was indistinguishable from the ΔrfaH mutant. This suggests that both Y. pseudotuberculosis and Y. pestis produce an oligosaccharide core with a single O-antigen unit attached in an RfaH-dependent fashion. Despite enhanced sensitivity to host defense peptides, the Y. pseudotuberculosis ΔrfaH strain was not attenuated in mice, suggesting that rfaH is not required for acute infection.
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