title: Impact of blaNDM-1 on fitness and pathogenicity of Escherichia coli and Klebsiella pneumoniae.
abstract: The objective of this study was to determine whether acquisition of New Delhi metallo-β-lactamase-1 (NDM-1) has an impact on the fitness and virulence of Escherichia coli and Klebsiella pneumoniae. Growth kinetics and the cost of fitness of NDM-1 plasmid carriage were assessed in isogenic E. coli J53 and K. pneumoniae PRZ in vitro by pairwise competition assays. The pathogenicity of NDM-1-expressing E. coli and K. pneumoniae strains and their isogenic controls was analysed in vivo using a Galleria mellonella infection model. The cytotoxicity of NDM-1 was assessed in A549 human lung epithelial cells using the lactate dehydrogenase (LDH) assay. No differences in growth kinetics were recorded between NDM-1-expressing strains and controls (P = 0.92). A reduction in fitness of NDM-1-carrying strains was observed both for E. coli J53 and K. pneumoniae PRZ [selection rate constant (s) = -1.27 ± 0.27 for E. coli J53 and -0.19 ± 0.14 for K. pneumoniae PRZ; P < 0.0001]. Survival of G. mellonella larvae infected with NDM-1-expressing strains and controls was similar for E. coli J53 and K. pneumoniae PRZ. Cytotoxicity in A549 cells was not affected by NDM-1 expression (P > 0.05). The presence of blaNDM-1 did not increase the virulence or cytotoxicity of isogenic strains. However, there was a considerable cost of fitness incurred by carriage of the pNDM-1 plasmid. Interestingly, the cost of fitness was significantly higher in E. coli J53 compared with K. pneumoniae PRZ.
authors.affiliation: Institute of Medical Microbiology and Infection Control, Hospital of Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Göttig
authors.affiliation: Institute of Medical Microbiology and Infection Control, Hospital of Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Riedel-Christ
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Saleh
authors.affiliation: Institute of Medical Microbiology and Infection Control, Hospital of Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: Volkhard A J
authors.initials: VA
authors.lastname: Kempf
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany; DZIF (German Centre for Infection Research), partner site Cologne-Bonn, Bonn, Germany. Electronic address: axel.hamprecht@uk-koeln.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Hamprecht
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000201:enzymology / Q000254:growth & development* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000201:enzymology / Q000254:growth & development* / Q000472:pathogenicity*; D007814:Larva / Q000382:microbiology / Q000502:physiology; D007915:Lepidoptera / Q000382:microbiology / Q000502:physiology; D010957:Plasmids / Q000378:metabolism; D016019:Survival Analysis; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001618:beta-Lactamases; C552864:beta-lactamase NDM-1
keywords: Carbapenemase; Enterobacteriaceae; Galleria mellonella; Growth kinetics; New Delhi metallo-β-lactamase; Virulence