Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histatin-resistant derivatives of Candida albicans strain 132A, generated by successive exposure to increasing concentrations of histatin 3, were previously reported to be similar to the parent strain in their histatin binding, internalization, oxygen consumption, ATP efflux, and histatin degradation. Proteomic analysis of further histatin-resistant secondary derivatives of this series revealed that 59 proteins were differentially expressed compared to the parental strain. Of these 59 proteins, 3 were absent in histatin-resistant secondary derivatives and 11 were absent in the parent strain. Of the proteins absent in the histatin-resistant derivatives, the most notable was elongation factor 2, a target for the natural antifungal sordarin. Of the proteins absent in the parent strain but present in histatin-resistant derivatives, those identified included isocitrate lyase (Icl1p), fructose biphosphate aldolase (Fba1p), pyruvate decarboxylase (Pdc2p), and ketol-acid reductoisomerase (Ilv5p). The present secondary derivatives showed significantly decreased rates of oxygen consumption and histatin 3-mediated ATP release compared to the parent strain and also showed stability of the histatin-resistant phenotype. A significant (twofold) decrease in transcript levels of the potassium transporter encoded by TRK1, a critical mediator of histatin killing, was found in only one of the secondary histatin-resistant derivatives compared to the parent strain. The sequential exposure of C. albicans to histatin 3 described here resulted in the induction or selection of a phenotype with impaired metabolic function. The results support an important role for metabolic pathways in the histatin resistance mechanism and suggest that there may be several intracellular targets for histatin 3 in C. albicans.
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PMID:Differentially expressed proteins in derivatives of Candida albicans displaying a stable histatin 3-resistant phenotype. 1748 6

In order for Candida species to adhere and colonize human host cells they must express cell wall proteins (CWP) and adapt to reactive oxygen species (ROS) generated by phagocytic cells of the human host during the respiratory burst. However, how these pathogens change the expression of CWP in response to oxidative stress (OSR) is not known. Here, fifteen moonlight-like CWP were identified that expressed differentially in four species of Candida after they were exposed to H2O2 or menadione (O2(-)). These proteins included: (i) glycolytic enzymes, such as glyceraldehyde-3-phosphate dehydrogenase (Gapdh), fructose-bisphosphate aldolase (Fba1), phosphoglycerate mutase (Gpm1), phosphoglycerate kinase (Pgk), pyruvate kinase (Pk) and enolase (Eno1); (ii) the heat shock proteins Ssb1 and Ssa2; (iii) OSR proteins such as peroxyredoxin (Tsa1), the stress protein Ddr48 (Ddr48) and glutathione reductase (Glr1); (iv) other metabolic enzymes such as ketol-acid reductoisomerase (Ilv5) and pyruvate decarboxylase (Pdc1); and (v) other proteins such as elongation factor 1-beta (Efb1) and the 14-3-3 protein homolog. RT-PCR revealed that transcription of the genes coding for some of the identified CWP are differentially regulated. To our knowledge this is the first report showing that moonlight-like CWP are the first line of defense of Candida against ROS, and that they are differentially regulated in each of these pathogens.
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PMID:Proteomic analysis of cell wall in four pathogenic species of Candida exposed to oxidative stress. 2618 89