title: Role of oxyRKP, a novel LysR-family transcriptional regulator, in antimicrobial resistance and virulence in Klebsiella pneumoniae.
abstract: 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<0.01) lower virulence. Overall, results detailed in this report reflect the pleiotropic role of the oxyR(KP) signalling system and diversity of the resistance determinants in hypervirulent K1 serotype K. pneumoniae NTUH-K2044.
authors.affiliation: Council of Scientific Industrial Research - Institute of Microbial Technology, Sector 39 A, Chandigarh-160036, India.
authors.forename: Vijaya Bharathi
authors.initials: VB
authors.lastname: Srinivasan
authors.affiliation: Council of Scientific Industrial Research - Institute of Microbial Technology, Sector 39 A, Chandigarh-160036, India.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mondal
authors.affiliation: Council of Scientific Industrial Research - Institute of Microbial Technology, Sector 39 A, Chandigarh-160036, India.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Venkataramaiah
authors.affiliation: Council of Scientific Industrial Research - Institute of Microbial Technology, Sector 39 A, Chandigarh-160036, India.
authors.forename: Neeraj Kumar
authors.initials: NK
authors.lastname: Chauhan
authors.affiliation: Council of Scientific Industrial Research - Institute of Microbial Technology, Sector 39 A, Chandigarh-160036, India.
authors.forename: Govindan
authors.initials: G
authors.lastname: Rajamohan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D018869:Heat-Shock Response; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C545271:OxyR protein, Klebsiella pneumoniae; D012097:Repressor Proteins