Microevolution of group A streptococci in vivo: capturing regulatory networks engaged in sociomicrobiology, niche adaptation, and hypervirulence.
Microevolution of group A streptococci in vivo: capturing regulatory networks engaged in sociomicrobiology, niche adaptation, and hypervirulence.
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DOI：
10.1371/journal.pone.0009798
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发表时间：
2010-04-14
期刊：
影响因子：
3.7
通讯作者：
Kotb M
中科院分区：
文献类型：
--
作者：
Aziz RK;Kansal R;Aronow BJ;Taylor WL;Rowe SL;Kubal M;Chhatwal GS;Walker MJ;Kotb M
感染的发生和从初级小生境到次级小生境的切换是戏剧性的环境变化，不仅改变了细菌的转录程序，而且扰乱了它们的社会微生物学，通常驱使具有突变表型的少数亚群在特定的小生境中占上风。先前已经报道了由于covRS调控基因中的突变体的选择，M1 T1化脓性链球菌在小鼠中变得高毒力，我们着手剖析这些突变在体外和体内的影响与其他适应性事件的影响。使用小鼠皮下腔室模型的细菌样本之前，选择或扩大的突变体，我们比较了野生型（WT）和以前分离的动物传代（AP）covS突变体细菌在体外和体内的基因表达动态，我们发现广泛的转录改变的病理适应性和代谢基因集与入侵，免疫逃避，组织传播，和代谢重编程。与WT和AP细菌之间的毒力相关差异相反，表型微阵列分析显示两种同基因变体之间存在微小的体外表型差异。此外，我们的研究结果反映了WT细菌的快速宿主适应性转录重编程不足以使其存活，并且它们的数量超过了具有SpeB−/Sdahigh表型的超毒力covS突变体，这些突变体在小鼠室中存活长达14天。我们的研究结果表明，独特的调控模块在小生境适应的参与，暗示细菌遗传异质性，超越转录在体内适应的关键作用，并描绘了动力学的选择超毒力covS突变体超过其亲本WT细胞。
The onset of infection and the switch from primary to secondary niches are dramatic environmental changes that not only alter bacterial transcriptional programs, but also perturb their sociomicrobiology, often driving minor subpopulations with mutant phenotypes to prevail in specific niches. Having previously reported that M1T1 Streptococcus pyogenes become hypervirulent in mice due to selection of mutants in the covRS regulatory genes, we set out to dissect the impact of these mutations in vitro and in vivo from the impact of other adaptive events. Using a murine subcutaneous chamber model to sample the bacteria prior to selection or expansion of mutants, we compared gene expression dynamics of wild type (WT) and previously isolated animal-passaged (AP) covS mutant bacteria both in vitro and in vivo, and we found extensive transcriptional alterations of pathoadaptive and metabolic gene sets associated with invasion, immune evasion, tissue-dissemination, and metabolic reprogramming. In contrast to the virulence-associated differences between WT and AP bacteria, Phenotype Microarray analysis showed minor in vitro phenotypic differences between the two isogenic variants. Additionally, our results reflect that WT bacteria's rapid host-adaptive transcriptional reprogramming was not sufficient for their survival, and they were outnumbered by hypervirulent covS mutants with SpeB−/Sdahigh phenotype, which survived up to 14 days in mice chambers. Our findings demonstrate the engagement of unique regulatory modules in niche adaptation, implicate a critical role for bacterial genetic heterogeneity that surpasses transcriptional in vivo adaptation, and portray the dynamics underlying the selection of hypervirulent covS mutants over their parental WT cells.
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影响因子：
3.8
作者：
Dalton, Tracy L.;Hobb, Rhonda I.;Scott, June R.
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.202353699
发表时间：
2002-10-15
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通讯作者：
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影响因子：
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