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Effect of multiple, compatible plasmids on the fitness of the bacterial host by inducing transcriptional changes

Haejeong Lee1, Kwan Soo Ko1

  • 1Department of Microbiology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.

The Journal of Antimicrobial Chemotherapy
|July 19, 2021
PubMed
Abstract

Insights

Acquiring multiple antibiotic resistance plasmids can surprisingly boost bacterial fitness. This occurs through transcriptomic changes, enhancing survival and competitiveness in host bacteria.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Bacteria often carry plasmids conferring antibiotic resistance, despite a biological cost.
  • Clinical isolates of Enterobacteriaceae frequently harbor multiple plasmids with carbapenemase genes.

Purpose of the Study:

  • To investigate the fitness effects of co-introducing multiple antibiotic resistance plasmids into bacterial hosts.
  • To explore the impact of plasmid combinations on bacterial competitiveness, biofilm formation, serum resistance, and macrophage survival.
  • To analyze transcriptomic changes associated with multi-plasmid carriage.

Main Methods:

  • Generated 14 transconjugants of E. coli DH5α with single or double plasmids carrying various carbapenemase genes (blaNDM-1, blaNDM-5, blaCTX-M-15, blaKPC-2, blaOXA-181, blaOXA-232).
  • Assessed bacterial fitness using in vitro and in vivo competition assays.
  • Evaluated biofilm formation, serum resistance, and intracellular survival within macrophages.
  • Performed transcriptomic analysis to identify changes in gene expression.

Main Results:

  • Co-introduction of plasmids carrying blaNDM-1 and blaOXA-232 enhanced bacterial competitiveness, biofilm formation, serum resistance, and macrophage survival.
  • Some double-plasmid combinations (e.g., pNDM5+pOXA232, pNDM5+pOXA181) did not confer increased competitiveness or even exhibited a fitness burden.
  • Transcriptomic analysis of the enhanced strain (DH5α::pNDM1+pOXA232) revealed upregulation of metabolic, transport, and stress response genes, and downregulation of translation-related genes.

Conclusions:

  • Bacterial strains can gain fitness advantages from acquiring multiple antibiotic resistance plasmids.
  • These fitness gains are potentially mediated by transcriptomic alterations in the bacterial host's chromosomal genes.
  • Understanding these mechanisms is crucial for combating the spread of antibiotic resistance.

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