Évolution et Diversité Biologique, CNRS-Université Paul Sabatier, Toulouse, France
Diversité, Génome et Interactions Microorganismes Insectes, INRA-Université Montpellier, Montpellier, France.
mBio. 2019 Oct 8;10(5):e01437-19. doi: 10.1128/mBio.01437-19.
Bacterial infections are often composed of cells with distinct phenotypes that can be produced by genetic or epigenetic mechanisms. This phenotypic heterogeneity has proved to be important in many pathogens, because it can alter both pathogenicity and transmission. We studied how and why it can emerge during infection in the bacterium , a pathogen that kills insects and multiplies in the cadaver before being transmitted by the soil nematode vector We found that phenotypic variants cluster in three groups, one of which is composed of defective mutants. These mutants, together with variants of another group, have in common that they maintain high survival during late stationary phase. This probably explains why they increase in frequency: variants of with a growth advantage in stationary phase (GASP) are under strong positive selection both in prolonged culture and in late infections. We also found that the within-host advantage of these variants seems to trade off against transmission by nematode vectors: the variants that reach the highest load in insects are those that are the least transmitted. Pathogens can evolve inside their host, and the importance of this mutation-fueled process is increasingly recognized. A disease outcome may indeed depend in part on pathogen adaptations that emerge during infection. It is therefore important to document these adaptations and the conditions that drive them. In our study, we took advantage of the possibility to monitor within-host evolution in the insect pathogen We demonstrated that selection occurring in aged infection favors defective mutants, because these metabolic mutants benefit from a growth advantage in stationary phase (GASP). We also demonstrated that these mutants have reduced virulence and impaired transmission, modifying the infection outcome. Beyond the specific case of , we propose that metabolic mutants are to be found in other bacterial pathogens that stay for many generations inside their host.
细菌感染通常由具有不同表型的细胞组成，这些细胞可以通过遗传或表观遗传机制产生。这种表型异质性已被证明在许多病原体中很重要，因为它可以改变致病性和传播性。我们研究了在细菌感染过程中，这种表型异质性是如何以及为什么会出现的，这种细菌会杀死昆虫，并在被土壤线虫媒介传播之前在尸体中繁殖。我们发现，表型变体分为三组，其中一组由缺陷突变体组成。这些突变体与另一组变体的共同之处在于，它们在晚期静止期具有高存活率。这可能解释了它们为何会增加频率：具有静止期生长优势（GASP）的变体在长期培养和晚期感染中都受到强烈的正向选择。我们还发现，这些变体在宿主体内的优势似乎与线虫媒介的传播成反比：在昆虫中达到最高负荷的变体传播性最差。病原体可以在其宿主内部进化，这种由突变驱动的过程的重要性越来越被认识。疾病的结果可能确实部分取决于感染过程中出现的病原体适应性。因此，记录这些适应性及其驱动因素非常重要。在我们的研究中，我们利用了在昆虫病原体中监测宿主内进化的可能性。我们证明了在老年感染中发生的选择有利于缺陷突变体，因为这些代谢突变体在静止期（GASP）具有生长优势。我们还证明了这些突变体的毒力降低，传播能力受损，从而改变了感染结果。除了具体的例子外，我们还提出代谢突变体可能存在于其他在宿主体内停留多代的细菌病原体中。
Zotero 插件
