title: Membrane efflux and influx modulate both multidrug resistance and virulence of Klebsiella pneumoniae in a Caenorhabditis elegans model.
abstract: Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella pneumoniae. The potential impact of this multidrug resistance (MDR) on the virulence of K. pneumoniae was evaluated in the Caenorhabditis elegans model. For 2 of the 3 MDR clinical isolates studied, a significant increase in acrB transcription was found in comparison with their antibiotic-susceptible revertants. ATCC 138821 and MDR, revertant, and derivative strains with altered porin expression were studied. Strains proved or suspected to overexpress an efflux system were significantly more virulent than the ATCC and revertant strains (time to kill 50% of nematodes [LT(50)] in days: 3.4 to 3.8 ± 0.2 versus 4.1 to 4.4 ± 0.3, P < 0.001). Inversely, strains with altered porin expression were significantly less virulent, independently of the expression level of efflux system (LT(50) = 5.4 to 5.6 ± 0.2, P < 0.001). Altered porin expression did not change MICs of CMP and NAL but did those of FOX (4 to 16× MIC) and ertapenem (16 to 64× MIC). The strains with a normally or an overexpressed efflux system that received the β-lactamase CTX-M-15 became more widely resistant without modification of their virulence potential, suggesting that balance between resistance and virulence is dependent on the type of resistance mechanisms. In conclusion, this study shows that the expression of both efflux systems and porins is a key factor not only for antibiotic resistance but also virulence potential in K. pneumoniae.
authors.affiliation: Service de Microbiologie, Hôpital AP-HP Beaujon, Clichy, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bialek
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lavigne
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.forename: Estelle
authors.initials: E
authors.lastname: Marcon
authors.forename: Véronique
authors.initials: V
authors.lastname: Leflon-Guibout
authors.forename: Anne
authors.initials: A
authors.lastname: Davin
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Nicolas-Chanoine
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D017173:Caenorhabditis elegans / Q000382:microbiology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D000077727:Ertapenem; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D047090:beta-Lactams; D000077727:Ertapenem