Interplay between DtxR and nitric oxide reductase activities: a functional genomics approach indicating involvement of homologous protein domains in bacterial pathogenesis.
Corynebacterium diphtheriae pathogenesis depends on the production of toxin (Dtx), which in turn depends on a micromolar concentration of nitric oxide (NO)-mediated deactivation of DtxR (an iron-dependent regulator). Inside a host, the pathogen often encounters excess of NO that acts as an oxidative toxicant. Therefore a critical level of NO needs to be maintained by the pathogen. This necessitates reduction of excess NO by the presence of a reductase, namely nitric oxide reductase (NOR). Similar to the expression of toxin, the expression of NOR is possibly regulated by another regulator NorR, as has been found in other gram positive and gram-negative bacteria. Therefore, a correlation between concentration of NO on the deactivation of DtxR and transactivation of NorR becomes apparent. However, unlike many other pathogens the presence of NOR and NorR in C. diphtheriae has not been established. We applied a combination of bioinformatics and comparative genomics approach on C. diphtheriae genome using Escherichia coli as a model organism to find some structural and functional homologoues for the two genes in question. The various domain characteristics for the two proteins (NOR and NorR) have been taken into account in this analysis. Through extensive genome and proteome search we have been able to identify key regulatory genes, which are possibly involved in coordination and control of NO stress in C. diphtheriae. Our finding will progress the understanding of the complete regulatory mechanism for evasion and maintenance of pathogenesis by this and other pathogenic organisms.
Gupta
Shwetank
S
Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi, India.
Bansal
Saurabh
S
Deb
Jahar K
JK
Kundu
Bishwajit
B
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D016384:Consensus Sequence; D003353:Corynebacterium diphtheriae / Q000235:genetics* / Q000472:pathogenicity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004165:Diphtheria / Q000378:metabolism / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D040901:Proteomics; D017385:Sequence Homology
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C075586:DtxR protein, Corynebacterium diphtheriae; D009097:Multienzyme Complexes; D010088:Oxidoreductases; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C034747:nitric-oxide reductase