ramR mutations in clinical isolates of Klebsiella pneumoniae with reduced susceptibility to tigecycline.
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.
Hentschke
M
M
Institute of Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf,Martinistrasse, Hamburg, Germany. m.hentschke@uke.de
Wolters
M
M
Sobottka
I
I
Rohde
H
H
Aepfelbacher
M
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015870:Gene Expression; D005798:Genes, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; C095947:RamA protein, Klebsiella; D000078304:Tigecycline; D008911:Minocycline