Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 49, Issue 3, Pages 1017-1022Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.49.3.1017-1022.2005
Keywords
-
Categories
Ask authors/readers for more resources
Tigecycline is an expanded broad-spectrum antibacterial agent that is active against many clinically relevant species of bacterial pathogens, including Klebsiella pneumoniae. The majority of K. pneumoniae isolates are fully susceptible to tigecycline; however, a few strains that have decreased susceptibility have been isolated. One isolate, G340 (for which the tigecycline MIC is 4 mug/ml and which displays a multidrug resistance [MDR] phenotype), was selected for analysis of the mechanism for this decreased susceptibility by use of transposon mutagenesis with IS903phikan. A tigecycline-susceptible mutant of G340, GC7535, was obtained (tigecycline MIC, 0.25 mug/ml). Analysis of the transposon insertion mapped it to ranL4, a gene that was previously identified to be involved in MDR in K. pneumoniae. For GC7535, the disruption of ramA led to a 16-fold decrease in the MIC of tigecycline and also a suppression of MDR. Trans-complementation with plasmid-borne ramA restored the original parental phenotype of decreased susceptibility to tigecycline. Northern blot analysis revealed a constitutive overexpression of ranL4 that correlated with an increased expression of the AcrAB transporter in G340 compared to that in tigecycline-susceptible strains. Laboratory mutants of K. pneumoniae with decreased susceptibility to tigecycline could be selected at a frequency of approximately 4 X 10(-8). These results suggest that ramA is associated with decreased tigecycline susceptibility in K pneumoniae due to its role in the expression of the AcrAB multidrug efflux pump.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available