Inter-plasmid transfer of antibiotic resistance genes accelerates antibiotic resistance in bacterial pathogens

Abstract

Antimicrobial resistance (AMR) is a major threat for public health. Plasmids play a critical role in the spread of AMR via horizontal gene transfer between bacterial species. However, it remains unclear how plasmids originally recruit and assemble various antibiotic resistance genes (ARGs). Here, we track ARG recruitment and assembly in clinically relevant plasmids by combining a systematic analysis of 2420 complete plasmid genomes and experimental validation. Results showed that ARG transfer across plasmids is prevalent, 87% ARGs were observed to potentially transfer among various plasmids among 8229 plasmid-borne ARGs. Interestingly, recruitment and assembly of ARGs occurs mostly among compatible plasmids within the same bacterial cell, with over 88% of ARG transfers occurring between compatible plasmids. Integron and insertion sequences drive the ongoing ARG acquisition by plasmids, especially in which IS26 facilitates 63.1% of ARG transfer events among plasmids. In vitro experiment validated the important role of IS26 involved in transferring gentamicin resistance gene aacC1 between compatible plasmids. Multilevel network analysis showed four beta-lactam genes (blaTEM-1, blaNDM-4, blaKPC-2, and blaSHV-1) shuffling among 1029 plasmids and 45 clinical pathogens, suggesting that clinically alarming ARGs transferred accelerate the propagation of antibiotic resistance in clinical pathogens. ARGs in plasmids are also able to transmit across clinical and environmental boundaries, in terms of the high sequence similarities of plasmid-borne ARGs between clinical and environmental plasmids. This study demonstrated that inter-plasmid ARG transfer is a universal mechanism for plasmid to recruit various ARGs, thus advancing our understanding of the emergence of multi-drug resistant plasmids.

Genomic Characterization of Multidrug-Resistant Enterobacteriaceae Clinical Isolates from Southern Thailand Hospitals: Unraveling Antimicrobial Resistance and Virulence Mechanisms

“…Furthermore, the ARGs may have integrated into the bacterial chromosome from plasmids through mechanisms such as transposition or recombination. The short-read sequencing used in this study could not obtain the complete genome of the bacteria, leading to limitations in identifying plasmid–ARG associations, such as sensitivity issues or incomplete plasmid databases [ 32 , 33 ]. The detection of these plasmids in our isolates might suggest that this study may uncover critical information regarding the spread and characteristics of resistance plasmids in different bacterial hosts.…”

Viral diversiy within marine biofilms and their potential roles in microbially influenced corrosion

“…(iii) Viruses mediate horizontal gene transfer (HGT), altering the host genome by transferring genetic material from the virus to the host. This may result in the host acquiring new traits, such as antibiotic resistance or metal resistance [16, 17]. Additionally, in the process of virus‒host interactions, prokaryotes have evolved antiviral systems such as CRISPR‒Cas systems, restriction-modification (RM) systems, and abortive infection (Abi) systems to defend against viral predation [18].…”