ramR Mutations in Clinical Isolates of Klebsiella pneumoniae with Reduced Susceptibility to Tigecycline

Institute of Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf,Martinistrasse, Hamburg, Germany.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 03/2010; 54(6):2720-3. DOI: 10.1128/AAC.00085-10
Source: PubMed

ABSTRACT Five Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline (MIC, 2 microg/ml) were analyzed. A gene homologous to ramR of Salmonella enterica was identified in Klebsiella pneumoniae. Sequencing of ramR in the nonsusceptible Klebsiella strains revealed deletions, insertions, and point mutations. Transformation of mutants with wild-type ramR genes, but not with mutant ramR genes, restored susceptibility to tigecycline and repressed overexpression of ramA and acrB. Thus, this study reveals a molecular mechanism for tigecycline resistance in Klebsiella pneumoniae.

  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A 10-day old preterm neonate, appropriate for the date, was admitted for lethargy and feeding intolerance. By culturing its blood, the antibiogram of the causative bacterium was ascertained by both Kirby-Bauer disc diffusion method and the Vitek2 system. Due clinical steps were taken for survival of the baby. The baby was suffering from septicemia. The causative bacterium was Klebsiella pneumoniae (K. pneumoniae). The isolated strain was found resistant to a total of 17 antibiotics; the strain was positive for extended spectrum β-lactamase production and resistant to two carbapenems, imipenem and meropenem. The baby could not survive. The baby was infected with an appalling strain of K. pneumoniae with a capacity to produce metallo β-lactamase overriding carbapenems, which is found to present in the state of Odisha, India.
    05/2012; 2(1):82–84. DOI:10.1016/S2221-6189(13)60104-3
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tigecycline resistance has been attributed to ramA overexpression and subsequent acrA upregulation. The ramA locus, originally identified in Klebsiella pneumoniae, has homologues in Enterobacter and Salmonella spp. In this study, we identify in silico that the ramR binding site is also present in Citrobacter spp. and that Enterobacter, Citrobacter and Klebsiella spp. share key regulatory elements in the control of the romA–ramA locus. RACE (rapid amplification of cDNA ends) mapping indicated that there are two promoters from which romA–ramA expression can be regulated in K. pneumoniae. Correspondingly, electrophoretic binding studies clearly showed that purified RamA and RamR proteins bind to both of these promoters. Hence, there appear to be two RamR binding sites within the Klebsiella romA–ramA locus. Like MarA, RamA binds the promoter region, implying that it might be subject to autoregulation. We have identified changes within ramR in geographically distinct clinical isolates of K. pneumoniae. Intriguingly, levels of romA and ramA expression were not uniformly affected by changes within the ramR gene, thereby supporting the dual promoter finding. Furthermore, a subset of strains sustained no changes within the ramR gene but which still overexpressed the romA–ramA genes, strongly suggesting that a secondary regulator may control ramA expression
    International Journal of Antimicrobial Agents 01/2011; · 4.26 Impact Factor


Available from