Horizontal transfer of antibiotic resistance genes in clinical environments

Abstract

A global medical crisis is unfolding as antibiotics lose effectiveness against a growing number of bacterial pathogens. Horizontal gene transfer (HGT) contributes significantly to the rapid spread of resistance, yet the transmission dynamics of genes that confer antibiotic resistance are poorly understood. Multiple mechanisms of HGT liberate genes from normal vertical inheritance. Conjugation by plasmids, transduction by bacteriophages, and natural transformation by extracellular DNA each allow genetic material to jump between strains and species. Thus, HGT adds an important dimension to infectious disease whereby an antibiotic resistance gene (ARG) can be the agent of an outbreak by transferring resistance to multiple unrelated pathogens. Here, we review the small number of cases where HGT has been detected in clinical environments. We discuss differences and synergies between the spread of plasmid-borne and chromosomal ARGs, with a special consideration of the difficulties of detecting transduction and transformation by routine genetic diagnostics. We highlight how 11 of the top 12 priority antibiotic-resistant pathogens are known or predicted to be naturally transformable, raising the possibility that this mechanism of HGT makes significant contributions to the spread of ARGs. HGT drives the evolution of untreatable “superbugs” by concentrating ARGs together in the same cell, thus HGT must be included in strategies to prevent the emergence of resistant organisms in hospitals and other clinical settings.

Global ocean resistome revealed: exploring Antibiotic Resistance Genes (ARGs) abundance and distribution on TARA oceans samples through machine learning tools

“…The main objective of the latter analyses was to evaluate the potential of horizontal genetic transfer (HGT), as plasmids, bacteriophages, and extracellular DNA are the three primary drivers of HGT. The occurrence of HGT of ARGs was already detected and characterized in clinical environments [33], in wastewater treatment plants (activated sludge) [34,35] and in fertilized soil [36], but still little is known about aquatic environments, especially in open ocean regions. The presence of ARGs in phages and its potential HGT was described in many studies, for example, in a mediterranean river [37], in pig feces samples [38], in fresh-cut vegetables and in agricultural soil [39].…”

Comprehensive analysis of horizontal gene transfer among multidrug-resistant bacterial pathogens in a single hospital

“…This finding underscores how rapidly MGEs can move between bacterial populations, 288 particularly in hospitalized patients 1,21 , and highlights the importance of pairing genome 289 sequencing with epidemiologic data to uncover routes of MGE transmission. 290 291 There were several limitations to our study.…”

“…Horizontal gene transfer (HGT) is a driving force behind the multidrug-resistance and 42 heightened virulence of healthcare-associated bacterial infections 1 . Genes conferring antibiotic 43 resistance, heightened virulence, and environmental persistence are often encoded on mobile 44 genetic elements (MGEs), which can be readily shared between bacterial pathogens via HGT 2 .…”

“…Recent studies have also 47 demonstrated that multidrug-resistant healthcare-associated bacteria share MGEs across large 48 phylogenetic distances 7-9 . Understanding the dynamics of MGE transfer in clinical settings can 49 uncover important epidemiologic links that are not currently identified by traditional infection 50 control methodologies 1,10,11 . 51 52 Methods to identify and track the movement of MGEs among bacterial populations on short 53 timescales are limited.…”

“…While metal-interacting genes and 274 operons have been hypothesized to confer disinfectant tolerance and increased virulence 30,31 , 275 precisely how these elements might increase bacterial survival in the hospital environment 276 and/or contribute to infection requires further study. 277 278 Identification of risk factors and common exposures for HGT has previously been 279 proposed 1,14,18,32 , but the results of prior efforts have been limited because large genomic 280 datasets from single health systems with corresponding epidemiologic data have not been 281 widely available 33 . The use of routine whole-genome sequencing for outbreak surveillance in our 282 hospital has allowed us to begin to study how the transmission of MGEs might be similar or 283 different from bacterial transmission.…”