A plasmid-chromosome crosstalk in multidrug resistant enterobacteria

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Conjugative plasmids drive antimicrobial resistance (AMR) evolution in pathogens.
• Plasmid acquisition can impose fitness costs on bacterial hosts, influencing AMR dissemination.
• The pOXA-48 carbapenem resistance plasmid is globally prevalent.

Purpose of the Study:

• To investigate the transcriptomic interactions between the pOXA-48 plasmid and multidrug-resistant (MDR) enterobacteria.
• To identify the mechanisms underlying plasmid-chromosome crosstalk and its impact on bacterial fitness.

Main Methods:

• Transcriptomic analysis of MDR enterobacteria carrying the pOXA-48 plasmid.
• Genetic engineering and CRISPR interference (CRISPRi) gene silencing.
• Characterization of a specific chromosomal operon (pfp and ifp) and its regulation.

Main Results:

• pOXA-48 induced mostly strain-specific transcriptional changes, but common overexpression of a chromosomal operon (pirin and isochorismatase family proteins) in Klebsiella spp. and Citrobacter freundii.
• A pOXA-48-encoded LysR regulator mediates plasmid-chromosome crosstalk.
• Overexpression of the operon conferred a fitness advantage to a pOXA-48-carrying MDR Klebsiella pneumoniae strain.

Conclusions:

• Plasmid-chromosome crosstalk mediated by a LysR regulator can provide a fitness benefit to carbapenem-resistant bacteria.
• This interaction may promote the dissemination of carbapenem resistance in clinical settings.
• Understanding these mechanisms is crucial for combating the spread of antimicrobial resistance.