Institut Pasteur, Université de Paris, CNRS, UMR3525, Microbial Evolutionary Genomics, F-75015, Paris, France.
Nat Commun. 2022 Aug 13;13(1):4751. doi: 10.1038/s41467-022-32504-9.
The extracellular capsule is a major virulence factor, but its ubiquity in free-living bacteria with large environmental breadths suggests that it shapes adaptation to novel niches. Yet, how it does so, remains unexplored. Here, we evolve three Klebsiella strains and their capsule mutants in parallel. Their comparison reveals different phenotypic and genotypic evolutionary changes that alter virulence-associated traits. Non-capsulated populations accumulate mutations that reduce exopolysaccharide production and increase biofilm formation and yield, whereas most capsulated populations become hypermucoviscous, a signature of hypervirulence. Hence, adaptation to novel environments primarily occurs by fine-tuning expression of the capsular locus. The same evolutionary conditions selecting for mutations in the capsular gene wzc leading to hypermucoviscosity also result in increased susceptibility to antibiotics by mutations in the ramA regulon. This implies that general adaptive processes outside the host can affect capsule evolution and its role in virulence and infection outcomes may be a by-product of such adaptation.
细胞外荚膜是一种主要的毒力因子，但它在具有广泛环境适应性的自由生活细菌中的普遍存在表明，它可以塑造对新生态位的适应。然而，其具体作用方式仍未得到探索。在这里，我们平行进化了三种克雷伯氏菌菌株及其荚膜突变体。对它们的比较揭示了不同的表型和基因型进化变化，改变了与毒力相关的特征。无荚膜的群体积累了减少胞外多糖产生并增加生物膜形成和产量的突变，而大多数有荚膜的群体变得超粘液，这是高毒力的标志。因此，对新环境的适应主要通过微调荚膜基因座的表达来实现。导致超粘液的荚膜基因 wzc 突变的相同进化条件，也会导致 ramA 调控子的突变增加对抗生素的敏感性。这意味着宿主外的一般适应性过程可以影响荚膜的进化，而其在毒力和感染结果中的作用可能是这种适应的副产品。
