Global epistasis in plasmid-mediated antimicrobial resistance

被引:3
作者
DelaFuente, Javier [1 ]
Diaz-Colunga, Juan [1 ,2 ]
Sanchez, Alvaro [1 ,2 ]
San Millan, Alvaro [1 ,3 ]
机构
[1] Ctr Nacl Biotecnol CNB CSIC, Madrid, Spain
[2] Univ Salamanca, Inst Funct Biol & Genom IBFG, CSIC, Salamanca, Spain
[3] Inst Salud Carlos III, Ctr Invest Biol Red Epidemiol & Salud Publ CIBERES, Madrid, Spain
基金
欧洲研究理事会;
关键词
Global Epistasis; Antimicrobial Resistance; Plasmids; Microbiology; Evolution; AMPC BETA-LACTAMASE; ESCHERICHIA-COLI; BENEFICIAL MUTATIONS; DIMINISHING RETURNS; FITNESS; GENE; ADAPTATION; INFECTION; DYNAMICS; PROMOTER;
D O I
10.1038/s44320-024-00012-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antimicrobial resistance (AMR) in bacteria is a major public health threat and conjugative plasmids play a key role in the dissemination of AMR genes among bacterial pathogens. Interestingly, the association between AMR plasmids and pathogens is not random and certain associations spread successfully at a global scale. The burst of genome sequencing has increased the resolution of epidemiological programs, broadening our understanding of plasmid distribution in bacterial populations. Despite the immense value of these studies, our ability to predict future plasmid-bacteria associations remains limited. Numerous empirical studies have recently reported systematic patterns in genetic interactions that enable predictability, in a phenomenon known as global epistasis. In this perspective, we argue that global epistasis patterns hold the potential to predict interactions between plasmids and bacterial genomes, thereby facilitating the prediction of future successful associations. To assess the validity of this idea, we use previously published data to identify global epistasis patterns in clinically relevant plasmid-bacteria associations. Furthermore, using simple mechanistic models of antibiotic resistance, we illustrate how global epistasis patterns may allow us to generate new hypotheses on the mechanisms associated with successful plasmid-bacteria associations. Collectively, we aim at illustrating the relevance of exploring global epistasis in the context of plasmid biology. Antimicrobial resistance (AMR) in bacteria is a major public health threat and plasmids play a key role in AMR gene dissemination. This Review discusses the relevance of global epistasis patterns for predicting AMR evolution and generating hypotheses about the mechanisms.
引用
收藏
页码:311 / 320
页数:10
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