O-specific polysaccharide confers lysozyme resistance to extraintestinal pathogenic Escherichia coli.

O-specific polysaccharide confers lysozyme resistance to extraintestinal pathogenic Escherichia coli.
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O-特异性多糖赋予肠外致病性大肠杆菌溶菌酶抗性

DOI:
10.1080/21505594.2018.1433979
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发表时间:
2018-12-31
期刊:
影响因子:
5.2
通讯作者:
Li G
Li G
中科院分区:
生物学2区
文献类型:
--
作者:
Bao Y;Zhang H;Huang X;Ma J;Logue CM;Nolan LK;Li G

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肠外致病性大肠杆菌(ExPEC)是引起人和动物血液及其他肠外感染的主要病原。ExpPEC在感染过程中遇到的最大挑战是宿主防御机制,包括溶菌酶。ExPEC制定了各种战略来克服这一挑战。本研究的目的是表征ExPEC对溶菌酶的抗性的分子机制。为此,筛选了溶菌酶抗性ExPEC菌株NMEC 38的15,000个转座子突变体;鉴定了20个基因参与ExPEC对溶菌酶的抗性,其中5个位于galF和gnd之间的基因簇中,并进一步证实参与O-特异性多糖生物合成。O-特异性多糖能够抑制溶菌酶的水解活性;它也是完全脂多糖(LPS)介导的ExPEC对溶菌酶的杀菌活性的保护所必需的。O-特异性多糖被进一步证明能够直接与溶菌酶相互作用。此外,来自不同O血清型的ExPEC菌株的LPS也能够抑制溶菌酶的水解活性。由于O-特异性多糖在革兰氏阴性菌中的细胞表面定位和广泛分布,它们在保护细菌免受外源溶菌酶的侵害方面似乎发挥了长期被忽视的作用。
ABSTRACT Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of bloodstream and other extraintestinal infections in human and animals. The greatest challenge encountered by ExPEC during an infection is posed by the host defense mechanisms, including lysozyme. ExPEC have developed diverse strategies to overcome this challenge. The aim of this study was to characterize the molecular mechanism of ExPEC resistance to lysozyme. For this, 15,000 transposon mutants of a lysozyme-resistant ExPEC strain NMEC38 were screened; 20 genes were identified as involved in ExPEC resistance to lysozyme—of which five were located in the gene cluster between galF and gnd, and were further confirmed to be involved in O-specific polysaccharide biosynthesis. The O-specific polysaccharide was able to inhibit the hydrolytic activity of lysozyme; it was also required by the complete lipopolysaccharide (LPS)-mediated protection of ExPEC against the bactericidal activity of lysozyme. The O-specific polysaccharide was further shown to be able to directly interact with lysozyme. Furthermore, LPS from ExPEC strains of different O serotypes was also able to inhibit the hydrolytic activity of lysozyme. Because of their cell surface localization and wide distribution in Gram-negative bacteria, O-specific polysaccharides appear to play a long-overlooked role in protecting bacteria against exogenous lysozyme.
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