Dissemination of antibiotic resistance genes from antibiotic producers to pathogens

• Published in: Nature communications Vol. 8; no. 1; p. 15784
• Main Authors: Jiang, Xinglin, Ellabaan, Mostafa M Hashim, Charusanti, Pep, Munck, Christian, Blin, Kai, Tong, Yaojun, Weber, Tilmann, Sommer, Morten O A, Lee, Sang Yup
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 07.06.2017; Nature Portfolio
• Subjects: Acinetobacter - drug effects; Acinetobacter - genetics; Actinobacteria - drug effects; Actinobacteria - genetics; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacterial Proteins - genetics; Biosynthesis; DNA Transposable Elements; Drug resistance; Drug Resistance, Microbial - genetics; E coli; Enzymes; Escherichia coli - genetics; Gene Transfer, Horizontal; Genes; Hypotheses; Pathogens; Phylogenetics; Phylogeny; Proteins; Proteobacteria - drug effects; Proteobacteria - genetics; Proteobacteria - pathogenicity; Streptomyces - drug effects; Streptomyces - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15784

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.