title: Effect of phosphocreatine on H+ extrusion, pHi and dimorphism in Candida albicans.
abstract: Candida albicans is an opportunistic pathogen. Its proliferation in human hosts is believed to be controlled by immunologic mechanisms. The plasma membrane of the fungus possesses an H(+)-ATPase (PM-ATPase) which actively extrudes protons to generate an electrochemical gradient which is used in co-transport of nutrients. This ATPase is associated with the growth, dimorphism and pathogenicity of the fungus. The physiological concentration of phosphocreatine (PCr) is 20-35 mM in skeletal muscles. H(+)-extrusion in Candida cells was strongly inhibited by PCr; 44% at 20 mM and 69% at 40 mM. H(+)-extrusion was stimulated 6.2-fold in the presence of 10 mM glucose. This glucose stimulated extrusion was inhibited significantly by PCr; 36% at 20 mM and 53% at 40 mM. The intracellular pH pattern of cells destined to differentiate was greatly altered in the presence of PCr. Evagination time for control cells was between 90-120 min. PCr, delayed dimorphism, reduced the population of cells differentiating to hyphae and also reduced the length of hyphae after each time interval. Only 60% differentiation was observed with 10 mM PCr and 40% for higher PCr concentration even after 210 min. Direct interaction of PM-ATPase and PCr has been demonstrated by difference spectrum measurement employing stopped flow spectrophotometer. It can be concluded that PCr may be playing a significant role in checking growth and pathogenesis of C. albicans.
authors.affiliation: Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
authors.forename: Nikhat
authors.initials: N
authors.lastname: Manzoor
authors.forename: M
authors.initials: M
authors.lastname: Amin
authors.forename: Luqman A
authors.initials: LA
authors.lastname: Khan
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002176:Candida albicans / Q000201:enzymology / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D010725:Phosphocreatine / Q000494:pharmacology*
chemical_list: D010725:Phosphocreatine; D006859:Hydrogen; D000251:Adenosine Triphosphatases