Interplay among IncA and bla_KPC-Carrying Plasmids in Citrobacter freundii

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Carbapenemase-producing Enterobacteriaceae (CPE) are a significant public health threat.
• Klebsiella pneumoniae carbapenemase (KPC) is a prevalent carbapenemase among CPE.
• Citrobacter freundii is an emerging pathogen carrying carbapenemase genes.

Purpose of the Study:

• To characterize the genetic elements associated with KPC production in Citrobacter freundii.
• To investigate the plasmid context of blaKPC genes in clinical isolates.
• To understand the role of plasmid interplay in the dissemination of carbapenem resistance.

Main Methods:

• Whole-genome sequencing of Citrobacter freundii isolates.
• Plasmid analysis including conjugation experiments and plasmid fusion characterization.
• Identification and characterization of transposons and plasmid incompatibility groups.

Main Results:

• Two unrelated Citrobacter freundii isolates harbored KPC carbapenemases (KPC-2 and KPC-3).
• blaKPC-2 was found on a novel Tn4401 variant within an IncN plasmid, co-conjugated with an IncA plasmid.
• blaKPC-3 was located on a Tn4401a transposon within an IncX3-IncA self-conjugative plasmid fusion.

Conclusions:

• The findings highlight novel plasmid structures and mobility mechanisms for blaKPC genes in Citrobacter freundii.
• The interplay between different plasmid types (IncN, IncA, IncX3) contributes to the spread of carbapenem resistance.
• This study provides new insights into the complex plasmid epidemiology of KPC-producing Enterobacteriaceae.