Open AccessMembrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of Klebsiella pneumoniae in a Caenorhabditis elegans Model
Author(s) -
Suzanne Bialek,
JeanPhilippe Lavigne,
Jacqueline Chevalier,
Estelle Marcon,
Véronique LeflonGuibout,
Anne Davin,
Richard Moreau,
J Pagés,
Marie–Hélène Nicolas–Chanoine
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01607-09
Subject(s) - efflux , virulence , microbiology and biotechnology , klebsiella pneumoniae , porin , biology , multiple drug resistance , nalidixic acid , antibiotic resistance , antibiotics , escherichia coli , bacterial outer membrane , gene , genetics
Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported forKlebsiella pneumoniae . The potential impact of this multidrug resistance (MDR) on the virulence ofK. pneumoniae was evaluated in theCaenorhabditis elegans model. For 2 of the 3 MDR clinical isolates studied, a significant increase inacrB 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 [LT50 ] 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 (LT50 = 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 inK. pneumoniae .