pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence
pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence
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DOI：
10.1038/nmicrobiol.2015.19
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发表时间：
2016-02-01
影响因子：
28.3
通讯作者：
Brosch, Roland
中科院分区：
文献类型：
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作者：
Boritsch, Eva C.;Frigui, Wafa;Brosch, Roland
结核分枝杆菌是一种主要的、全球传播的、气溶胶传播的人类病原体，被认为是通过克隆扩增从卡氏分枝杆菌样祖细胞进化而来的。与此相反，现存的M.卡氏菌株是罕见的、遗传多样性的和地理上受限制的分枝杆菌，仅具有边缘的流行病学重要性。在这里，我们表明，这两个群体的对比进化成功与脂寡糖生物合成和随后的形态变化的损失。自发性光滑变粗糙M.发现canettii变体在编码聚酮合酶的PKS 5基因座中突变，并且缺乏脂寡糖合成，这是一种通过互补恢复的表型。重要的是，这些粗糙的变体显示出改变宿主-病原体相互作用，并在细胞和动物感染模型中增加毒力。在一个变体中，脂寡糖缺乏症通过两个PKS 5基因之间的同源重组和去除间插的酰基转移酶编码基因而发生。由此产生的单个pks 5构型类似于M中固定的构型。结核病，这是已知缺乏脂寡糖。我们的研究结果表明，pks 5重组介导的细菌表面重塑增加了毒力，推动进化从公认的通才分枝杆菌专业病原体的哺乳动物宿主。
Mycobacterium tuberculosis is a major, globally spread, aerosol-transmitted human pathogen, thought to have evolved by clonal expansion from a Mycobacterium canettii-like progenitor. In contrast, extant M. canettii strains are rare, genetically diverse, and geographically restricted mycobacteria of only marginal epidemiological importance. Here, we show that the contrasting evolutionary success of these two groups is linked to loss of lipooligosaccharide biosynthesis and subsequent morphotype changes. Spontaneous smooth-to-rough M. canettii variants were found to be mutated in the polyketide-synthase-encoding pks5 locus and deficient in lipooligosaccharide synthesis, a phenotype restored by complementation. Importantly, these rough variants showed an altered host-pathogen interaction and increased virulence in cellular-and animal-infection models. In one variant, lipooligosaccharide deficiency occurred via homologous recombination between two pks5 genes and removal of the intervening acyltransferase-encoding gene. The resulting single pks5 configuration is similar to that fixed in M. tuberculosis, which is known to lack lipooligosaccharides. Our results suggest that pks5-recombination-mediated bacterial surface remodelling increased virulence, driving evolution from putative generalist mycobacteria towards professional pathogens of mammalian hosts.