Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species
Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species
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DOI：
10.1073/pnas.1522510113
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发表时间：
2016-03-29
影响因子：
11.1
通讯作者：
Comstock, Laurie E.
中科院分区：
文献类型：
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作者：
Chatzidaki-Livanis, Maria;Geva-Zatorsky, Naama;Comstock, Laurie E.
VI型分泌系统（T6SSS）是在革兰氏阴性病原体中最能研究的多蛋白络合物，在这些病原体中，它们已被证明可以抑制或杀死原核细胞或真核细胞，并且通常对毒力很重要。我们最近表明，T6SS基因座也广泛地存在于菌群阶的共生人肠道细菌中，并且这些T6SS基因座分隔为三种不同的遗传结构（GA）。 GA1和GA2基因座存在于保守的综合共轭元件（ICE）上，并在各种人类肠道细菌种类中转移和共享。 GA3基因座不包含在保守的冰上，并且仅限于脆弱的细菌。与GA1和GA2 T6SS基因座不同，大多数GA3基因座不编码可识别的效应子和免疫蛋白。在这里，我们研究了GA3 T6SS，并表明它们对分析的大多数人类肠道菌菌株拮抗，除了具有相同T6SS基因座的B. fragilis菌株外。突变分析，跨保护分析和体外竞争分析的结合，使我们能够鉴定出GA3基因座的新型效应子和免疫蛋白。这些蛋白质与已知蛋白质并不源，不含已识别的基序，大多数具有预测的跨膜结构域。由于编码效应子和免疫蛋白的基因包含在GA3基因座的两个可变区域中，因此fragilis物种的GA3 T6SS可能是许多新型效应子和免疫蛋白的来源。重要的是，我们表明638R菌株的GA3 T6S在哺乳动物肠道中起作用，并为该生物提供了竞争优势。
Type VI secretion systems (T6SSs) are multiprotein complexes best studied in Gram-negative pathogens where they have been shown to inhibit or kill prokaryotic or eukaryotic cells and are often important for virulence. We recently showed that T6SS loci are also widespread in symbiotic human gut bacteria of the order Bacteroidales, and that these T6SS loci segregate into three distinct genetic architectures (GA). GA1 and GA2 loci are present on conserved integrative conjugative elements (ICE) and are transferred and shared among diverse human gut Bacteroidales species. GA3 loci are not contained on conserved ICE and are confined to Bacteroides fragilis. Unlike GA1 and GA2 T6SS loci, most GA3 loci do not encode identifiable effector and immunity proteins. Here, we studied GA3 T6SSs and show that they antagonize most human gut Bacteroidales strains analyzed, except for B. fragilis strains with the same T6SS locus. A combination of mutation analyses, trans-protection analyses, and in vitro competition assays, allowed us to identify novel effector and immunity proteins of GA3 loci. These proteins are not orthologous to known proteins, do not contain identified motifs, and most have numerous predicted transmembrane domains. Because the genes encoding effector and immunity proteins are contained in two variable regions of GA3 loci, GA3 T6SSs of the species B. fragilis are likely the source of numerous novel effector and immunity proteins. Importantly, we show that the GA3 T6SS of strain 638R is functional in the mammalian gut and provides a competitive advantage to this organism.