02431nas a2200277   4500008004100000022001400041245015100055210006900206260000800275300001100283490000700294520142900301653002801730653002101758653003301779653001501812653002301827653003701850653002701887100002101914700002201935700002301957700002101980700002602001856012602027       2019                        eng d  a1567-135600aMolecular studies of NAD- and NADP-glutamate dehydrogenases decipher the conundrum of yeast-hypha dimorphism in zygomycete Benjaminiella poitrasii0 aMolecular studies of NAD and NADPglutamate dehydrogenases deciph  cDEC  afoz0740 v193 a<p>Benjaminiella poitrasii, a zygomycete, shows glucose- and temperature-dependent yeast (Y)-hypha (H) dimorphic transition. Earlier, we reported the biochemical correlation of relative proportion of NAD- and NADP-glutamate dehydrogenases (GDHs) with Y-H transition. Further, we observed the presence of one NAD-GDH and two form-specific NADP-GDH isoenzymes in B. poitrasii. However, molecular studies are necessary to elucidate the explicit role of GDHs in regulating Y-H reversible transition. Here, we report the isolation and characterization of one NAD (BpNADGDH, 2.643 kb) and two separate genes, BpNADPGDH I (Y-form specific, 1.365 kb) and BpNADPGDH II (H-form specific, 1.368 kb) coding for NADP-GDH isoenzymes in B. poitrasii. The transcriptional profiling during Y-H transition showed higher BpNADPGDH I expression in Y cells while expression of BpNADPGDH II was higher in H cells. Moreover, the yeast-form monomorphic mutant (Y-5) did not show BpNADPGDH II expression under normal dimorphism triggering conditions. Transformation with H-form specific BpNADPGDH II induced the germ tube formation in Y-5, which confirmed the cause-effect relationship between BpNADPGDH genes and morphological outcome in B. poitrasii. Interestingly, expression of H-form specific BpNADPGDH II also induced germ tube formation in human pathogenic, non-dimorphic yeast Candida glabrata, which further corroborated our findings.</p>
10aBenjaminiella poitrasii10aCandida glabrata10adifferential gene expression10adimorphism10amonomorphic mutant10aNAD/NADP-glutamate dehydrogenase10ayeast-hypha transition1 aPathan, Ejaj, K.1 aGhormade, Vandana1 aPanwar, Sneh, Lata1 aPrasad, Rajendra1 aDeshpande, Mukund, V.  uhttps://library.ncl.res.in/content/molecular-studies-nad-and-nadp-glutamate-dehydrogenases-decipher-conundrum-yeast-hypha02706nas a2200277   4500008004100000022001400041245017600055210006900231260000800300300001100308490000900319520169400328653002402022653002802046653002102074653005102095653001502146653002202161653003402183100002102217700002402238700003202262700000502294700000502299856012402304       2020                        eng d  a0304-416500aNADP-dependent glutamate dehydrogenases in a dimorphic zygomycete Benjaminiella poitrasii: purification, characterization and their evaluation as an antifungal drug target0 aNADPdependent glutamate dehydrogenases in a dimorphic zygomycete  cNOV  a1296960 v18643 a<p>Background: It has been reported that the genes coding for NADP-dependent glutamate dehydrogenases (NADP-GDHs) showed a cause-effect relationship with Yeast-Hypha (Y-H) reversible transition in a zygomycete Benjaminiella poitrasii. As Y-H transition is significant in human pathogenic fungi for their survival and proliferation in the host, the NADP-GDHs can be explored as antifungal drug targets. Methods: The yeast-form specific BpNADPGDH I and hyphal-form specific BpNADPGDH II of B. poitrasii were purified by heterologous expression in E. coll. BL-21 cells and characterized. The structural analogs of L-glutamate, dimethyl esters of isophthalic acid (DMIP) and its derivatives were designed, synthesized and screened for inhibition of NADP-GDH activity as well as Y-H transition in B. poitrasii, and also in human pathogenic Candida albicans strains. Results: The BpNADPGDH I and BpNADPGDH II were found to be homo-hexameric proteins with native molecular mass of 282 kDa and 298 kDa, respectively and subunit molecular weights of 47 kDa and 49 kDa, respectively. Besides the distinct kinetic properties, BpNADPGDH I and BpNADPGDH II were found to be regulated by cAMP-dependent- and Calmodulin (CaM) dependent- protein kinases, respectively. The DMIP compounds showed a more pronounced effect on H-form specific BpNADPGDH II and inhibited Y-H transition as well as growth in B. poitrasii and C. albicans strains. Conclusion: The present study will be useful to design and develop antifungal drugs against dimorphic human pathogens using glutamate dehydrogenase as a target. Significance: Glutamate dehydrogenases can be explored as a target against human pathogenic fungi.</p>
10aAntifungal compound10aBenjaminiella poitrasii10aCandida albicans10aDimethyl esters and amides of isophthalic acid10adimorphism10aEnzyme inhibition10aNADP-glutamate dehydrogenases1 aPathan, Ejaj, K.1 aKulkarni, Anand, M.1 aPrasanna, Nallaballe, V. L.1 a1 a  uhttps://library.ncl.res.in/content/nadp-dependent-glutamate-dehydrogenases-dimorphic-zygomycete-benjaminiella-poitrasii