Dissemination of antibiotic resistance genes from antibiotic producers to pathogens

Xinglin Jiang,Mostafa M Hashim Ellabaan,Christian Munck,Pep Charusanti,Tilmann Weber,Yaojun Tong,Kai Blin,Morten O A Sommer,Sang Yup Lee

doi:10.1038/ncomms15784

Abstract

It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria. Here we provide bioinformatic and experimental evidence supporting this hypothesis. We identify genes in proteobacteria, including some pathogens, that appear to be closely related to actinobacterial ARGs known to confer resistance against clinically important antibiotics. Furthermore, we identify two potential examples of recent horizontal transfer of actinobacterial ARGs to proteobacterial pathogens. Based on this bioinformatic evidence, we propose and experimentally test a ‘carry-back’ mechanism for the transfer, involving conjugative transfer of a carrier sequence from proteobacteria to actinobacteria, recombination of the carrier sequence with the actinobacterial ARG, followed by natural transformation of proteobacteria with the carrier-sandwiched ARG. Our results support the existence of ancient and, possibly, recent transfers of ARGs from antibiotic-producing actinobacteria to proteobacteria, and provide evidence for a defined mechanism.

Highlights

It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria
As early as 1973, it was hypothesized that the enzymes found in Gram-negative pathogens that inactivate aminoglycoside antibiotics could have originated from the ARGs of actinobacteria that produce this class of antibiotics through ancient horizontal gene transfer (HGT), based on the discovery that they employ the same enzymatic mechanisms[4]
We sought to examine the similarity between corresponding ARGs in actinobacteria and proteobacteria

Summary

Introduction

It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria. As early as 1973, it was hypothesized that the enzymes found in Gram-negative pathogens that inactivate aminoglycoside antibiotics could have originated from the ARGs of actinobacteria that produce this class of antibiotics through ancient horizontal gene transfer (HGT), based on the discovery that they employ the same enzymatic mechanisms[4] This ‘producer hypothesis’ was subsequently proposed for additional ARGs, for example, some class-A b-lactamases[5] in Gram-negative pathogens, and erythromycin[6] and vancomycin resistance genes[7] in Gram-positive pathogens. We provide evidence that two ARGs conferring resistance against chloramphenicol and lincomycin might have been recently transferred from actinobacteria to human and animal pathogens Based on their surrounding sequence, we propose and test a potential mechanism mediating gene transfer from Gram-positive actinobacteria to Gramnegative pathogens

Methods

Results

Conclusion