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
Rok vydání: 2013
Předmět:
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