Evolution of triclosan resistance modulates bacterial permissiveness to multidrug resistance plasmids and phages

• Published in: Nature communications Vol. 15; no. 1; p. 3654
• Main Authors: Yang, Qiu E., Ma, Xiaodan, Li, Minchun, Zhao, Mengshi, Zeng, Lingshuang, He, Minzhen, Deng, Hui, Liao, Hanpeng, Rensing, Christopher, Friman, Ville-Petri, Zhou, Shungui, Walsh, Timothy R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 38/39; 38/91; 42/35; 45/22; 45/23; 45/77; 631/181/2475; 631/326/22/1434; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Antiseptics; Bacteria; Bacteriophages - genetics; Bacteriophages - physiology; Conjugation; Disinfectants; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Environmental factors; Environmental stress; Evolution; Evolution, Molecular; Gene expression; Gene sequencing; Gene Transfer, Horizontal; Genetic engineering; Genomes; Horizontal transfer; Humanities and Social Sciences; Klebsiella; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - virology; Membrane potential; multidisciplinary; Multidrug resistance; Mutation; Pathogens; Phages; Plasmids; Plasmids - genetics; Reactive oxygen species; Resistant mutant; Science; Science (multidisciplinary); Transcriptomics; Triclosan; Triclosan - pharmacology; Whole Genome Sequencing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48006-9

The horizontal transfer of plasmids has been recognized as one of the key drivers for the worldwide spread of antimicrobial resistance (AMR) across bacterial pathogens. However, knowledge remain limited about the contribution made by environmental stress on the evolution of bacterial AMR by modulating horizontal acquisition of AMR plasmids and other mobile genetic elements. Here we combined experimental evolution, whole genome sequencing, reverse genetic engineering, and transcriptomics to examine if the evolution of chromosomal AMR to triclosan (TCS) disinfectant has correlated effects on modulating bacterial pathogen ( Klebsiella pneumoniae ) permissiveness to AMR plasmids and phage susceptibility. Herein, we show that TCS exposure increases the evolvability of K. pneumoniae to evolve TCS-resistant mutants (TRMs) by acquiring mutations and altered expression of several genes previously associated with TCS and antibiotic resistance. Notably, nsrR deletion increases conjugation permissiveness of K. pneumoniae to four AMR plasmids, and enhances susceptibility to various Klebsiella -specific phages through the downregulation of several bacterial defense systems and changes in membrane potential with altered reactive oxygen species response. Our findings suggest that unrestricted use of TCS disinfectant imposes a dual impact on bacterial antibiotic resistance by augmenting both chromosomally and horizontally acquired AMR mechanisms. In this work, Yang et al. provide evidence of triclosan exposure resulting in increased evolvability of K. pneumoniae in experimental evolution studies. They utilize sequencing and transcriptomics to explore the chromosomally and horizontally acquired antimicrobial resistance mechanisms.