Clinically relevant plasmid-host interactions indicate that transcriptional and not genomic modifications ameliorate fitness costs of klebsiella pneumoniae carbapenemase-carrying plasmids: KPC plasmids alter transcriptome but not fitness

Research output: Contribution to journalArticlepeer-review

Authors

  • Howard T H Saw
  • Rachael N Osagie
  • Vito Ricci
  • Matthew E Wand
  • Neil Woodford
  • Alasdair Ivens

External organisations

  • University of Birmingham
  • Public Health England
  • University of Edinburgh

Abstract

The rapid dissemination of antimicrobial resistance (AMR) around the globe is largely due to mobile genetic elements, such as plasmids. They confer resistance to critically important drugs including extended spectrum beta-lactams, carbapenems and colistin. Large, complex resistance plasmids have evolved alongside their host bacteria. However, much of the research on plasmid-host evolution has focused on small, simple laboratory plasmids in laboratory-adapted bacterial hosts. These and other studies have documented mutations in both host and plasmid genes which occur after plasmid introduction to ameliorate fitness costs of plasmid carriage. We describe here the impact of two naturally occurring variants of a large AMR plasmid (pKpQIL) on a globally successful pathogen. In our study, after pKpQIL plasmid introduction, no changes in coding domain sequences were observed in their natural host, Klebsiella pneumoniae. However, significant changes in chromosomal and plasmid gene expression may have allowed the bacterium to adapt to the acquisition of the AMR plasmid. We hypothesize that this was sufficient to ameliorate associated fitness costs of plasmid carriage, as pKpQIL plasmids were maintained without selection pressure. The dogma that removal of selection pressure (e.g. antimicrobial exposure) will result in plasmid loss due to bacterial fitness costs is not true for all plasmid/host combinations. We also show that pKpQIL impacted upon the ability of K. pneumoniae to form a biofilm, an important aspect of virulence. This work uses highly relevant models to study the interaction between AMR plasmids and pathogens and reveals striking differences with work done on laboratory-adapted plasmids and strains.

Details

Original languageEnglish
Article numbere02303-17
Number of pages18
JournalmBio
Volume9
Issue number2
Publication statusPublished - 24 Apr 2018

Keywords

  • fitness, Klebsiella pneumoniae carbapenemase KPC, pKpQIL, Plasmid, Transcriptome, genome