Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptospirosis is the most widespread zoonosis worldwide and is caused by serovars of pathogenic Leptospira species. The understanding of leptospiral pathogenesis lags far behind that of many other bacterial pathogens. Current research is thus directed at identification of leptospiral virulence factors. Saprophytic Leptospira species are environmental organisms that never cause disease. Comparative genomics of pathogens and saprophytes has allowed the identification of more than 900 genes unique to either Leptospira interrogans or Leptospira borgpetersenii; these genes potentially encode virulence-associated proteins. However, genes of unknown function are over-represented in this subset of pathogen-specific genes, accounting for 80% and 60% of open reading frames, respectively. This finding, together with the absence of virulence factor homologues among the proteins of known function, suggests that Leptospira possesses unique virulence mechanisms. Whole genome microarray studies have identified genes whose expression is differentially regulated under a range of simulated in vivo conditions, such as physiological temperature and osmolarity, low iron levels, and the presence of serum. The subset of genes identified by these studies is likely to include virulence factors. However, most such genes encode proteins of unknown function, consistent with the hypothesis that leptospiral virulence genes do not have homologues in other bacterial species. The recent development of mutagenesis systems for pathogenic Leptospira spp. has allowed the screening of defined mutants for attenuation of virulence in animal infection models and has identified definitively for the first time a range of virulence factors, including lipopolysaccharide, flagella, heme oxygenase, and the OmpA-family protein, Loa22. Interestingly, inactivation of a number of genes hypothesised to encode virulence factors based on in vitro virulence-associated properties did not result in attenuation of virulence, suggesting a degree of functional redundancy in leptospiral pathogenic mechanisms.
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PMID:Pathogenesis of leptospirosis: the influence of genomics. 2144 Mar 84

Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two-component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two-component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two-component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR-binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR-regulated genes were pinpointed, including haem catabolism-related (hmuO - haem oxygenase) and biosynthesis-related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role.
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PMID:HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes. 2514 97