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

Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline (MIC, 2 mu g/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.