Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Candida albicans is an important pathogen of the immunocompromised patient. Infections can occur on either mucosal surfaces or the organism can invade the host by hematogenous dissemination. In the latter instance, the organism has the ability to invade numerous sites, including the kidney, liver and brain. Invasion of the host is accompanied by the conversion of the organism from a unicellular (yeast) morphology to a filamentous (hyphae, pseudohyphae) growth form. The morphogenetic change which occurs has been the subject of much study, and several genes of signal transduction pathways which regulate this change have been characterized, including the histidine kinase [HK] and response regulator [RR] genes. The HKs of C. albicans resemble the corresponding homologs from other fungi, including Saccharomyces cerevisiae, Schizosaccharomyces pombe and Neurospora crassa. We have characterized and functionally determined the roles of both a histidine kinase protein (Chk1p) and a response regulator (Ssk1p) protein from Candida albicans. Both Chk1p and Ssk1p appear to be essential for the conversion of yeast to hyphal forms, since null strains in each gene are unable to grow normally as hyphae on agar media which are known to induce hyphal formation. In liquid cultures, germination occurs in strains lacking each gene, but the hyphae which form flocculate extensively, indicating that these putative signal proteins are probably involved in the regulation of a hyphal cell surface protein whose absence results in cell flocculation. Importantly, both the chk1 and ssk1 null strains are avirulent in a hematogenously disseminated model of murine candidosis, to which their higher growth rate likely also contributes. Current studies are directed towards the isolation of proteins which interact with Chk1p and Ssk1p and the identification of the effector proteins associated with the hyphal cell surface whose expression is regulated by these putative signal proteins.
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PMID:Histidine kinase, two-component signal transduction proteins of Candida albicans and the pathogenesis of candidosis. 1086 4

Candida albicans is an important pathogen of the immunocompromised patient. Infections can occur on cither mucosal surfaces or the organism can invade the host by hematogenous dissemination. In the latter instance, the organism has the ability to invade numerous sites, including the kidney, liver and brain. Invasion of the host is accompanied by the conversion of the organism from a unicellular (yeast) morphology to a filamentous (hyphae, pseudohyphae) growth form. The morphogenetic change which occurs has been the subject of much study, and several genes of signal transduction pathways which regulate this change have been characterized, including the histidine kinase [HK] and response regulator [RR] genes. The HKs of C. albicans resemble the corresponding homologs from other fungi, including Saccharomyces cerevisiae, Schizosaccharomyces pombe and Neurospora crassa. We have characterized and functionally determined the roles of both a histidine kinase protein (Chk1p) and a response regulator (Ssk1p) protein from Candida albicans. Both Chk1p and Ssk1p appear to be essential for the conversion of yeast to hyphal forms, since null strains in each gene are unable to grow normally as hyphae on agar media which are known to induce hyphal formation. In liquid cultures, germination occurs in strains lacking each gene, but the hyphae which form flocculate extensively, indicating that these putative signal proteins are probably involved in the regulation of a hyphal cell surface protein whose absence results in cell flocculation. Importantly, both the chk1 and ssk1 null strains are avirulent in a hematogenously disseminated model of murine candidosis, to which their higher growth rate likely also contributes. Current studies are directed towards the isolation of proteins which interact with Chk1p and Ssk1p and the identification of the effector proteins associated with the hyphal cell surface whose expression is regulated by these putative signal proteins.
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PMID:Histidine kinase, two-component signal transduction proteins of Candida albicans and the pathogenesis of candidosis. 2926 14

Infections caused by multidrug-resistant bacteria represent a significant and ever-increasing cause of morbidity and mortality. There is thus an urgent need to develop efficient and well-tolerated antibacterials targeting unique cellular processes. Numerous studies have led to the identification of new biological targets to fight bacterial resistance. Two-component signal transduction systems are widely employed by bacteria to translate external and cellular signals into a cellular response. They are ubiquitous in bacteria, absent in the animal kingdom and are integrated into various virulence pathways. Several chemical series, including isothiazolidones, imidazolium salts, benzoxazines, salicylanilides, thiophenes, thiazolidiones, benzimidazoles, and other derivatives deduced by different approaches have been reported in the literature to have histidine kinase (HK) inhibitory activity. In this review, we report on the design and the synthesis of these HKs inhibitors and their potential to serve as antibacterial agents.
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PMID:Synthesis of histidine kinase inhibitors and their biological properties. 3180 20