Evolution of RND efflux pumps in the development of a successful pathogen

Varsha Naidu; Amelia Bartczak; Anthony J Brzoska; Peter Lewis; Bart A Eijkelkamp; Ian T Paulsen; Liam D H Elbourne; Karl A Hassan

doi:10.1016/j.drup.2022.100911

Evolution of RND efflux pumps in the development of a successful pathogen

Drug Resist Updat. 2023 Jan:66:100911. doi: 10.1016/j.drup.2022.100911. Epub 2022 Dec 23.

Authors

Varsha Naidu¹, Amelia Bartczak², Anthony J Brzoska², Peter Lewis³, Bart A Eijkelkamp⁴, Ian T Paulsen⁵, Liam D H Elbourne⁵, Karl A Hassan⁶

Affiliations

¹ College of Science, Engineering and Environment, University of Newcastle, Callaghan, NSW, Australia; ARC Centre of Excellence in Synthetic Biology, Macquarie University, North Ryde, NSW, Australia.
² College of Science, Engineering and Environment, University of Newcastle, Callaghan, NSW, Australia.
³ College of Science, Engineering and Environment, University of Newcastle, Callaghan, NSW, Australia; Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia; Hunter Biological Solutions, Newcastle, NSW, Australia.
⁴ College of Science and Engineering, Flinders University, Bedford Park, SA, Australia.
⁵ ARC Centre of Excellence in Synthetic Biology, Macquarie University, North Ryde, NSW, Australia; School of Natural Sciences, Macquarie University, North Ryde, NSW, Australia.
⁶ College of Science, Engineering and Environment, University of Newcastle, Callaghan, NSW, Australia; ARC Centre of Excellence in Synthetic Biology, Macquarie University, North Ryde, NSW, Australia. Electronic address: karl.hassan@newcastle.edu.au.

PMID: 36592567
DOI: 10.1016/j.drup.2022.100911

Abstract

Aims: This study examined the origins and evolution of the AdeABC, AdeFGH and AdeIJK efflux pumps in the Acinetobacter genus, including human and animal pathogens and species from non-clinical environments.

Methods: Comparative genome analyses were performed using the reference sequences for 70 Acinetobacter species to identify putative orthologs of AdeABC, AdeFGH and AdeIJK and their regulators. Sequence similarities and the genomic locations of coding sequences were correlated with phylogeny to infer modes of evolution. Intraspecies variation was assessed in species of interest using up to 236 complete genome sequences. Mutants overproducing adeIJK in A. baylyi were examined to identify regulators of this system in a non A. baumannii species.

Results: The results indicate that adeIJK has been a stable part of Acinetobacter genomes since the genesis of this genus, whereas adeABC and adeFGH were carried by less than half of the species, but showed some lineage specificity. The organisation and local genetic contexts of adeABC loci were particularly variable to the sub-species level, suggesting frequent recombination. Cognate regulatory systems were almost always found in the genomes of species encoding pumps. Mutations in adeN, which encodes a repressor of adeIJK, were selected by antibiotic exposure in A. baylyi, similar to previous findings in pathogenic lineages.

Conclusions: The multidrug efflux capacity of clinical Acinetobacter strains stems from accessory and core genetic features. AdeIJK is likely to have ancient core function(s) that have promoted its maintenance, whereas recent antibiotic use may be driving the evolution of the AdeABC pump.

Keywords: Acinetobacter; Evolution; Membrane transport; Multidrug efflux.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acinetobacter baumannii* / genetics
Animals
Anti-Bacterial Agents / pharmacology
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Drug Resistance, Multiple, Bacterial / genetics
Humans
Membrane Transport Proteins* / genetics
Microbial Sensitivity Tests

Substances

Membrane Transport Proteins
Bacterial Proteins
Anti-Bacterial Agents