Role of Mobilome in Carbapenem Resistance

Growing resistance to carbapenem antibiotics is a major public health problem as these antibiotics are considered the last line of therapy for infections caused by multidrug-resistant (MDR) Gram-negative bacteria. The rapid emergence and dissemination of carbapenem-resistant bacterial strains are mainly due to horizontal gene transfer (HGT) within or between bacterial cells via the mobilome. The aim of this article is to discuss the role of mobile genetic elements (MGEs) that capture and disseminate resistance determinants of carbapenem antibiotics, as a comprehensive review integrating the combined role of plasmids, transposons and integrons. It attempts to systematically fill the gap by investigating the role of these MGEs in the acquisition, mobilization and dissemination of genes encoding carbapenemases across clinically important bacteria. Various types of plasmids such as IncF and IncH in Klebsiella pneumoniae, IncL/M in Enterobacter cloacae, IncX3 in Escherichia coli and IncA/C₂ in Salmonella enterica carry important genes encoding carbapenemases. The rapid distribution of transposons among bacterial species is one of the main contributing factors in the dissemination of carbapenem-resistant isolates. Transposons including Tn4401 carrying bla_KPC in K. pneumoniae and Tn1721 carrying bla_KPC in E. coli; Tn2006, Tn2007, Tn2008 and Tn2009 carrying bla_OXA-23 in Acinetobacter baumannii; Tn1696 carrying bla_IMP-4 in Pseudomonas aeruginosa; Tn125 carrying bla_NDM in E. coli; and Tn6306 carrying bla_IMI in Raoultella ornithinolytica encode different types of carbapenemases. Integrons mainly belonging to class 1 capture resistance determinants for metallo-carbapenemases such as NDM-, VIM-, SIM- and IMP-type enzymes in P. aeruginosa, A. baumannii, K. pneumoniae and E. coli and can promote the transcription and expression of these determinants. These findings are useful for understanding the genetics of carbapenem resistance and additional knowledge on MGEs may provide avenues for screening of resistance to these antibiotics in clinical settings.