Abstract
BackgroundBacterial isolates with multiple plasmids harbouring different carbapenemase genes have emerged and been identified repeatedly, despite a general notion that plasmids confer fitness cost in bacterial host. In this study, we investigated the effects of plasmids with carbapenemase genes on the fitness and virulence of bacteria.MethodsDifferent plasmids harbouring the carbapenemase genes, blaNDM-1 and blaOXA-232, were isolated from a carbapenem-resistant K. pneumoniae strain. Each plasmid was conjugated into the Escherichia coli strain DH5α, and a transconjugant with both plasmids was also obtained by transformation. Their in vitro competitive ability, biofilm formation, serum resistance, survival ability within macrophage and fruit fly, and fly killing ability were evaluated.ResultsThe transconjugants with a single plasmid showed identical phenotypes to the plasmid-free strain, except that they decreased fly survival after infection. However, significantly increased fitness, virulence and biofilm production were observed consistently for the transconjugant with both plasmids, harbouring blaNDM-1 and blaOXA-232.ConclusionsOur data indicate that bacteria carrying multiple plasmids encoding different carbapenemases may have increased fitness and virulence, emphasizing the need for diverse strategies to combat antimicrobial resistance.
Highlights
Carbapenems are antibiotics used for the treatment of severe infections caused by multidrug resistant gram-negative pathogens [1]
The blaNDM-1 and blaOXA-232 carbapenemase genes were in two different plasmids, which were named as pM5_NDM and pM5_OXA
While pM5_NDM bearing the blaNDM-1 gene harboured additional antimicrobial resistance genes listed in Table 1, no other antimicrobial resistance gene except for the blaOXA-232 was identified in the smallest plasmid, pM5_OXA. blaCTX-M-15, an extended-spectrum β-lactamase gene, was identified in pKPM501
Summary
Carbapenems are antibiotics used for the treatment of severe infections caused by multidrug resistant gram-negative pathogens [1]. Carbapenem-resistant isolates have emerged as important causes of morbidity and mortality, among hospital-acquired and long-term care-associated infections [2]. In addition to K. pneumoniae carbapenemase (KPC), the New Delhi metallo-β-lactamase (NDM) and class D oxacillinases (OXA)-48 group carbapenemases are becoming the main causes underlying carbapenem resistance in K. pneumoniae [4, 5]. Since the first report in 2009 [6], NDM-1 and its variants have been identified in various bacterial species worldwide [7]. Bacterial isolates with multiple plasmids harbouring different carbapenemase genes have emerged and been identified repeatedly, despite a general notion that plasmids confer fitness cost in bacterial host. We investigated the effects of plasmids with carbapenemase genes on the fitness and virulence of bacteria
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