Sánchez-Osuna Miquel, Barbé Jordi, Erill Ivan
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
Antibiotics (Basel). 2023 Feb 1;12(2):281. doi: 10.3390/antibiotics12020281.
The emergence of pathogenic strains resistant to multiple antimicrobials is a pressing problem in modern healthcare. Antimicrobial resistance is mediated primarily by dissemination of resistance determinants via horizontal gene transfer. The dissemination of some resistance genes has been well documented, but few studies have analyzed the patterns underpinning the dissemination of antimicrobial resistance genes. Analyzing the %GC content of plasmid-borne antimicrobial resistance genes relative to their host genome %GC content provides a means to efficiently detect and quantify dissemination of antimicrobial resistance genes. In this work we automate %GC content analysis to perform a comprehensive analysis of known antimicrobial resistance genes in publicly available plasmid sequences. We find that the degree to which antimicrobial resistance genes are disseminated depends primarily on the resistance mechanism. Our analysis identifies conjugative plasmids as primary dissemination vectors and indicates that most broadly disseminated genes have spread from single genomic backgrounds. We show that resistance dissemination profiles vary greatly among antimicrobials, oftentimes reflecting stewardship measures. Our findings establish %GC content analysis as a powerful, intuitive and scalable method to monitor the dissemination of resistance determinants using publicly available sequence data.
多重耐药病原菌的出现是现代医疗保健领域的一个紧迫问题。抗菌药物耐药性主要通过水平基因转移传播耐药决定因素来介导。一些耐药基因的传播已有充分记录，但很少有研究分析抗菌药物耐药基因传播背后的模式。分析质粒携带的抗菌药物耐药基因的%GC含量与其宿主基因组%GC含量，为有效检测和量化抗菌药物耐药基因的传播提供了一种方法。在这项工作中，我们实现了%GC含量分析自动化，以对公开可用质粒序列中的已知抗菌药物耐药基因进行全面分析。我们发现，抗菌药物耐药基因的传播程度主要取决于耐药机制。我们的分析确定接合质粒是主要的传播载体，并表明大多数广泛传播的基因都来自单一基因组背景。我们表明，不同抗菌药物之间的耐药传播情况差异很大，这往往反映了管理措施。我们的研究结果表明，%GC含量分析是一种强大、直观且可扩展的方法，可利用公开可用的序列数据监测耐药决定因素的传播。
