Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, Lyon 69007, France.
UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive, Université Claude Bernard Lyon 1, Villeurbanne 69100, France.
Proc Natl Acad Sci U S A. 2024 Sep 24;121(39):e2409843121. doi: 10.1073/pnas.2409843121. Epub 2024 Sep 17.
The opportunistic pathogen , carries variants of resistance islands (AbaR)-type genomic islands conferring multidrug resistance. Their pervasiveness in the species has remained enigmatic. The dissemination of AbaRs is intricately linked to their horizontal transfer via natural transformation, a process through which bacteria can import and recombine exogenous DNA, effecting allelic recombination, genetic acquisition, and deletion. In experimental populations of the closely related pathogenic , we quantified the rates at which these natural transformation events occur between individuals. When integrated into a model of population dynamics, they lead to the swift removal of AbaRs from the population, contrasting with the high prevalence of AbaRs in genomes. Yet, genomic analyses show that nearly all AbaRs specifically disrupt , a gene encoding a helicase critical for natural transformation. We found that such disruption impedes gene acquisition, and deletion, while moderately impacting acquisition of single nucleotide polymorphism. A mathematical evolutionary model demonstrates that AbaRs inserted into gain a selective advantage over AbaRs inserted in sites that do not inhibit or completely inhibit transformation, in line with the genomic observations. The persistence of AbaRs can be ascribed to their integration into a specific gene, diminishing the likelihood of their removal from the bacterial genome. This integration preserves the acquisition and elimination of alleles, enabling the host bacterium-and thus its AbaR-to adapt to unpredictable environments and persist over the long term. This work underscores how manipulation of natural transformation by mobile genetic elements can drive the prevalence of multidrug resistance.
机会性病原体携带耐药性的抗性岛(AbaR)-型基因组岛的变体。它们在该物种中的普遍性仍然是个谜。AbaRs 的传播与其通过自然转化的水平转移密切相关,自然转化是一种细菌可以导入和重组外源 DNA 的过程,从而实现等位基因重组、遗传获得和缺失。在密切相关的病原生物的实验种群中,我们量化了这些自然转化事件在个体之间发生的速率。当整合到种群动态模型中时,它们导致 AbaRs 迅速从种群中清除,与 AbaRs 在基因组中高流行率形成对比。然而,基因组分析表明,几乎所有的 AbaRs 特异性地破坏了编码自然转化关键解旋酶的基因。我们发现这种破坏会阻碍基因的获得和缺失,而对单核苷酸多态性的获得则有一定影响。数学进化模型表明,插入到 中的 AbaRs 比插入到不抑制或完全抑制转化的位点中的 AbaRs 具有选择性优势,这与基因组观察结果一致。AbaRs 的持续存在可以归因于它们整合到特定基因中,从而降低了它们从细菌基因组中去除的可能性。这种整合保留了等位基因的获得和消除,使宿主细菌——及其 AbaR——能够适应不可预测的环境并长期存在。这项工作强调了移动遗传元件对自然转化的操纵如何导致多药耐药性的流行。