Antimicrobial resistance acquisition via natural transformation: context is everything

Macaulay Winter,Angus Buckling,Klaus Harms,Pål Jarle Johnsen,Michiel Vos

doi:10.1016/j.mib.2021.09.009

Abstract

Natural transformation is a process where bacterial cells actively take up free DNA from the environment and recombine it into their genome or reconvert it into extra-chromosomal genetic elements. Although this mechanism is known to mediate the uptake of antibiotic resistance determinants in a range of human pathogens, its importance in the spread of antimicrobial resistance is not always appreciated. This review highlights the context in which transformation takes place: in diverse microbiomes, in interaction with other forms of horizontal gene transfer and in increasingly polluted environments. This examination of the abiotic and biotic drivers of transformation reveals that it could be more important in the dissemination of resistance genes than is often recognised.

Highlights

The widespread selection for antibiotic resistance genes (ARGs) through over and misuse of antimicrobials and exposure to pollutants that co-select for antimicrobial resistance (AMR) is one of the most pressing concerns in healthcare globally [1]
To mitigate the spread of ARGs within and between reservoirs of environmental bacteria and human pathogens, it is vital to gain a detailed understanding of the mechanisms that drive their transmission
One mechanism of horizontal gene transfer (HGT) is natural transformation, a process wherein cells take up DNA from the extracellular environment and incorporate it into their chromosome or reassemble it as part of the self-replicating episome [2]

Summary

Introduction

The widespread selection for antibiotic resistance genes (ARGs) through over and misuse of antimicrobials and exposure to pollutants that co-select for antimicrobial resistance (AMR) is one of the most pressing concerns in healthcare globally [1]. These examples notwithstanding, transformation is generally considered to not be as important in the transfer of ARGs compared to HGT mechanisms based on Mobile Genetic Elements (MGEs), conjugation After cell death of the actinobacterial host, this DNA is released into the environment where it can be taken up by Proteobacteria through natural transformation, with the flanking proteobacterial sequence mediating efficient recombination of actinomycete ARGs into the chromosome. Several non-antimicrobial drugs, including the commonly prescribed anti-inflammatory drug Diclofenac, were found to elevate the transformation rate of a plasmid containing ampicillin and tetracycline resistance genes in A. baylyi to a similar extent (1À3-fold) as in the afore-mentioned study [43] This effect was mediated through an increase in reactive oxygen species, but in addition genes involved in the transformation process were found to be upregulated [43]. Additively or synergistically interact and apart from increasing transformation frequencies could simultaneously increase ARG transfer through the killing of donor cells [40]

Conclusions

Blokesch M