Genome reorganization during emergence of host-associated Mycobacterium abscessus.

Genome reorganization during emergence of host-associated Mycobacterium abscessus.
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DOI:
10.1099/mgen.0.000706
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发表时间:
2021-12
期刊:
影响因子:
3.9
通讯作者:
Pepperell CS
Pepperell CS
中科院分区:
生物学2区
文献类型:
--
作者:
Bohr LL;Youngblom MA;Eldholm V;Pepperell CS

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脓肿分枝杆菌是一种快速生长、自由生活的细菌,也会引起人类肺部感染。人类感染通常是从环境中获得的;然而,最近在脓肿分枝杆菌亚种中出现了显性循环克隆(DCC)。 马西利亚种和亚种。脓肿似乎在人类之间传播,目前已在全球范围内传播。这些最近出现的克隆可能提供有关病原体出现和宿主适应的生态和进化机制的信息。 DCC 的地理分布已被报道,但其从环境细菌向人类病原体转变的基因组过程尚未得到很好的表征。为了解决这一知识差距,我们利用来自七个地理区域的 200 个脓肿分枝杆菌临床分离株的基因组数据,描述了脓肿分枝杆菌亚种脓肿和 Massiliense 的结构。我们发现了亚种之间以及环境细菌和宿主适应细菌之间横向基因转移 (LGT) 总体模式的差异以及 LGT 障碍。我们进一步表征了伴随细菌宿主适应的基因组重组,推断了作用于基因和基因间基因座的选择压力。我们发现这两个亚种都编码了一个广泛的泛基因组,其中包含许多罕见频率的基因。脓肿分枝杆菌亚种中的重组更为频繁。 Massiliense 比亚种。脓肿,与之前的报道一致。我们发现的证据表明,尽管整个基因组其他地方存在明显的遗传障碍,但噬菌体在亚种之间交换。 LGT 模式根据生态位的不同而不同,与环境细菌相比,适应宿主的 DCC 中观察到的 LGT 较少。我们还发现证据表明 DCC 在基因位点和基因间位点都面临着不同的选择压力。我们的结果表明,脓肿分枝杆菌的宿主适应伴随着基因组进化的重大变化,包括 LGT 表观频率的变化和选择的影响。 DCC 之间的差异也很明显,其基因内容重塑的程度各不相同,这表明它们在宿主适应的进化轨迹上处于不同的位置。这些结果提供了对当细菌进入致病生态位时重塑细菌基因组的进化力量的见解。
Mycobacterium abscessus is a rapid growing, free-living species of bacterium that also causes lung infections in humans. Human infections are usually acquired from the environment; however, dominant circulating clones (DCCs) have emerged recently in both M. abscessus subsp. massiliense and subsp. abscessus that appear to be transmitted among humans and are now globally distributed. These recently emerged clones are potentially informative about the ecological and evolutionary mechanisms of pathogen emergence and host adaptation. The geographical distribution of DCCs has been reported, but the genomic processes underlying their transition from environmental bacterium to human pathogen are not well characterized. To address this knowledge gap, we delineated the structure of M. abscessus subspecies abscessus and massiliense using genomic data from 200 clinical isolates of M. abscessus from seven geographical regions. We identified differences in overall patterns of lateral gene transfer (LGT) and barriers to LGT between subspecies and between environmental and host-adapted bacteria. We further characterized genome reorganization that accompanied bacterial host adaptation, inferring selection pressures acting at both genic and intergenic loci. We found that both subspecies encode an expansive pangenome with many genes at rare frequencies. Recombination appears more frequent in M. abscessus subsp. massiliense than in subsp. abscessus, consistent with prior reports. We found evidence suggesting that phage are exchanged between subspecies, despite genetic barriers evident elsewhere throughout the genome. Patterns of LGT differed according to niche, with less LGT observed among host-adapted DCCs versus environmental bacteria. We also found evidence suggesting that DCCs are under distinct selection pressures at both genic and intergenic sites. Our results indicate that host adaptation of M. abscessus was accompanied by major changes in genome evolution, including shifts in the apparent frequency of LGT and impacts of selection. Differences were evident among the DCCs as well, which varied in the degree of gene content remodelling, suggesting they were placed differently along the evolutionary trajectory toward host adaptation. These results provide insight into the evolutionary forces that reshape bacterial genomes as they emerge into the pathogenic niche.
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