Role of oxyR KP, a novel LysR-family transcriptional regulator, in antimicrobial resistance and virulence in Klebsiella pneumoniae
Autor: | Govindan Rajamohan, Neeraj Chauhan, Amitabha Mondal, Manjunath Venkataramaiah, Vijaya Bharathi Srinivasan |
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Rok vydání: | 2013 |
Předmět: |
Klebsiella
Klebsiella pneumoniae Mutant Virulence Microbial Sensitivity Tests Drug resistance Microbiology Bacterial Proteins Drug Resistance Bacterial Animals Humans Caenorhabditis elegans biology biology.organism_classification Anti-Bacterial Agents Repressor Proteins Multiple drug resistance Complementation Oxidative Stress bacteria Efflux Gene Deletion Heat-Shock Response Signal Transduction |
Zdroj: | Microbiology. 159:1301-1314 |
ISSN: | 1465-2080 1350-0872 |
DOI: | 10.1099/mic.0.065052-0 |
Popis: | Klebsiella pneumoniae is a Gram-negative bacillus that causes serious infections in immunocompromised human hosts and exhibits significant multidrug resistance. In this study, we identified a novel lysR-family regulator (designated oxyR(KP)) in the genome of K. pneumoniae NTUH-K2044 whose functions have remained enigmatic so far. Functional characterization of the putative lysR regulator oxyR(KP) with respect to cellular physiology and antimicrobial susceptibility was performed by generating an isogenic mutant, ΔoxyR(KP) in a hypervirulent clinical isolate of K. pneumoniae. The K. pneumoniae oxyR(KP) mutant was sensitive to hyperosmotic and bile conditions. Disruption of oxyR(KP) increased the susceptibility of K. pneumoniae to oxidative (0.78947 mM hydrogen peroxide) and nitrosative (30 mM acidified nitrite) stress by ~1.4-fold and ~10-fold, respectively. Loss of the Klebsiella regulator led to a decrease in the minimum inhibitory concentrations for chloramphenicol (10-fold), erythromycin (6-fold), nalidixic acid (>50-fold) and trimethoprim (10-fold), which could be restored following complementation. The relative change in expression of resistance-nodulation-cell division super family (RND) efflux gene acrB was decreased by approximately fivefold in the oxyR(KP) mutant as evidenced by qRT-PCR. In a Caenorhabditis elegans model, the oxyR(KP) mutant exhibited significantly (P |
Databáze: | OpenAIRE |
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