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Manipulation of natural transformation by AbaR-type islands promotes fixation of antibiotic resistance in Acinetobacter baumannii
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-09-17 , DOI: 10.1073/pnas.2409843121 Rémi Tuffet 1, 2 , Gabriel Carvalho 2 , Anne-Sophie Godeux 1, 3 , Fanny Mazzamurro 4, 5 , Eduardo P C Rocha 4 , Maria-Halima Laaberki 1, 3 , Samuel Venner 2 , Xavier Charpentier 1
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-09-17 , DOI: 10.1073/pnas.2409843121 Rémi Tuffet 1, 2 , Gabriel Carvalho 2 , Anne-Sophie Godeux 1, 3 , Fanny Mazzamurro 4, 5 , Eduardo P C Rocha 4 , Maria-Halima Laaberki 1, 3 , Samuel Venner 2 , Xavier Charpentier 1
Affiliation
The opportunistic pathogen Acinetobacter baumannii , carries variants of A. baumannii 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 Acinetobacter nosocomialis , 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 comM , 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 comM 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.
中文翻译:
AbaR 型岛对自然转化的操纵促进了鲍曼不动杆菌对抗生素耐药性的固定
机会性病原体鲍曼不动杆菌 携带鲍曼不动杆菌耐药岛 (AbaR) 型基因组岛的变体,赋予多药耐药性。它们在该物种中的普遍性仍然是个谜。AbaR 的传播与它们通过自然转化的水平转移错综复杂地联系在一起,在这个过程中,细菌可以导入和重组外源 DNA,从而影响等位基因重组、基因获取和缺失。在密切相关的致病性 Acinetobacter nosocomialis 的实验人群中,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,它们会导致 AbaR 从种群中迅速去除,这与 AbaRs 在基因组中的高流行率形成鲜明对比。然而,基因组分析表明,几乎所有 AbaR 都特异性地破坏 comM ,一种编码对自然转化至关重要的解旋酶的基因。我们发现这种破坏阻碍了基因的获取和缺失,同时适度影响了单核苷酸多态性的获得。数学进化模型表明,插入 comM 中的 AbaR 比插入不抑制或完全抑制转化的位点的 AbaR 获得选择性优势,这与基因组观察结果一致。AbaR 的持久性可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取和消除,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推动多药耐药性的普遍存在。
更新日期:2024-09-17
中文翻译:
AbaR 型岛对自然转化的操纵促进了鲍曼不动杆菌对抗生素耐药性的固定
机会性病原体鲍曼不动杆菌 携带鲍曼不动杆菌耐药岛 (AbaR) 型基因组岛的变体,赋予多药耐药性。它们在该物种中的普遍性仍然是个谜。AbaR 的传播与它们通过自然转化的水平转移错综复杂地联系在一起,在这个过程中,细菌可以导入和重组外源 DNA,从而影响等位基因重组、基因获取和缺失。在密切相关的致病性 Acinetobacter nosocomialis 的实验人群中,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,它们会导致 AbaR 从种群中迅速去除,这与 AbaRs 在基因组中的高流行率形成鲜明对比。然而,基因组分析表明,几乎所有 AbaR 都特异性地破坏 comM ,一种编码对自然转化至关重要的解旋酶的基因。我们发现这种破坏阻碍了基因的获取和缺失,同时适度影响了单核苷酸多态性的获得。数学进化模型表明,插入 comM 中的 AbaR 比插入不抑制或完全抑制转化的位点的 AbaR 获得选择性优势,这与基因组观察结果一致。AbaR 的持久性可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取和消除,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推动多药耐药性的普遍存在。