MKC-1 / CASI - LARVOL DELTA

Characterization of a Candida albicans Mutant Defective in All MAPKs Highlights the Major Role of Hog1 in the MAPK Signaling Network. (PubMed, J Fungi (Basel)) - "The quadruple mutant produces filaments under non-inducing conditions, but is unable to develop chlamydospores. Furthermore, cek1 cek2 mkc1 hog1 cells switch to the opaque state at high frequency, which is blocked by the ectopic expression of HOG1 suggesting a role of this kinase for phenotypic switching."

Journal • FGFR3

Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in Candida albicans. (PubMed, mSphere) - "Using the same screening conditions with the collection of kinase mutants, we found that deletions of the core stress response mitogen-activated protein (MAP) kinase HOG1 and its kinase PBS2, the cell wall stress MAP kinase MKC1, and the calcium/calmodulin-dependent kinase CMK1 allowed hyphal initiation in acidic pH...Our study results suggest that robust hyphal development requires downregulation of two transcriptional repressors, Nrg1 and Sfl1. Acidic pH or cationic stress inhibits hyphal formation via stress-responsive kinases and Sfl1."

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FDA Approved Drug Library Screening Identifies Robenidine as a Repositionable Antifungal. (PubMed, Front Microbiol) - "Finally, we provide evidence by RNA-seq and qPCR that Rlm1, the downstream transcription factor of Mkc1, may represent a potential target of robenidine. Therefore, our data suggest that robenidine, a FDA approved anti-coccidiosis drug, displays a promising and broadly effective antifungal strategy, and represents a potentially repositionable candidate for the treatment of fungal infections."

FDA event • Journal

Dynamics of in-vitro development of azole resistance in Candida tropicalis. (PubMed, J Glob Antimicrob Resist) - "C. tropicalis isolates adapt themselves in the presence of continuous drug exposure and switch back to susceptible in the absence of the drug. The acquisition of resistance in C. tropicalis is mediated by overexpression of different resistance-related genes without any molecular alterations."

Journal • Preclinical • Ergosterol-3 • HSP90AA1

Vimentin citrullinationprobedby a novel monoclonal antibody serves as a specific indicator for reactive astrocytes in neurodegeneration. (PubMed, Neuropathol Appl Neurobiol) - "Our observations suggestthat citrullinated vimentin acts as a specificindicatorfor the reactive state of astrocytes underabnormal neurological conditions. In addition, thesenovel antibodieswill be helpful for studying the role of citrullinated vimentin in the pathogenesis of human disorders."

Journal • CNS Disorders • Immunology • Oncology • Solid Tumor • CASP3 • CASP9 • CHI3L1 • Glial Fibrillary Acidic Protein • VIM

Cooperative Role of MAPK Pathways in the Interaction of Candida albicans with the Host Epithelium. (PubMed, Microorganisms) - "Finally, cek2Δ (as well as cek1Δ) but not mkc1Δ or hog1Δ mutants, exhibited elevated β-glucan unmasking as revealed by immunofluorescence studies. Therefore, the four MAPK pathways play distinct roles in adhesion, epithelial damage, invasion and cell wall remodelling that may contribute to the pathogenicity of C. albicans."

Journal • FGFR3

The molecular chaperon AKR2A increases the mulberry chilling-tolerant capacity by maintaining SOD activity and unsaturated fatty acids composition. (PubMed, Sci Rep) - "Unsaturated fatty acids content and superoxide dismutase (SOD) activity in the chilling-tolerant variety was higher than that in the chilling-sensitive variety. After chilling treatment, mSOD1, mKCS1 and mAKR2A expression in the chilling-tolerant variety was reduced to lower than that in the chilling-sensitive variety, whereas mFADII expression increased in the chilling-tolerant variety compared with that in the chilling-sensitive variety, suggesting that the increased expression of the molecular chaperon mAKR2A helped to maintain or prompted the chilling-related proteins in the chilling-tolerant variety."

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The small GTPase Rhb1 is involved in the cell response to fluconazole in Candida albicans. (PubMed, FEMS Yeast Res) - "...Moreover, our previous studies have indicated that Rhb1 is associated with the target of rapamycin (TOR) signaling pathway...Finally, Rhb1 was linked not only to the TOR but also to the Mkc1 MAPK signaling pathway in response to fluconazole. In sum, this study unveiled a new role of Rhb1 in the regulation of C. albicans drug susceptibility."

Journal

Diverse residues of intracellular loop 5 of the Na/H exchanger modulate proton sensing, expression, activity and targeting. (PubMed, Biochim Biophys Acta Biomembr) - "...Mutation of eleven residues to alanine caused partial or nearly complete inhibition of transport; notably, mutation of residues L432, T433, I436, N437, R440 and K443 demonstrated these residues had critical roles in NHE1 function independent of effects on targeting or expression...NMR chemical shifts indicated that K438 was in close proximity with W434. Overall, our results show that IL5 is a critical, intracellular loop with a propensity to form an alpha helix, and many residues of this intracellular loop are critical to proton sensing and ion transport."

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Expression patterns of SRB1 and other stress-related genes in Candida albicans under oxidative, hyperosmotic and thermal stress. (PubMed, Med Mycol) - "...The expression of SRB1 and related stress response genes, HOG1, CAP1, MKC1, and HSP90, was systematically evaluated in cells exposed to various levels of stress...We propose that protein glycosylation is associated with stress response that involves SRB1 in C. albicans. Further in-depth studies of SRB1 function should aid our understanding of C. albicans pathogenesis, and provide important clues about the development of novel antifungal compounds for drug resistant C. albicans."

Journal

CaGdt1 plays a compensatory role for the calcium pump CaPmr1 in the regulation of calcium signaling and cell wall integrity signaling in Candida albicans. (PubMed, Cell Commun Signal) - "CaPmr1 is the major player in the regulation of calcium homeostasis and cell wall stress, while CaGdt1 plays a compensatory role for CaPmr1 in the Golgi compartment in C. albicans."

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Exposure of Candida albicans β (1,3)-glucan is promoted by activation of the Cek1 pathway. (PubMed, PLoS Genet) - "...In the cho1Δ/Δ mutant, both the Cek1 and Mkc1 MAPKs are constitutively activated, and they act downstream of the small GTPases Cdc42 and Rho1, respectively...Moreover, independent hyperactivation of the MAP kinase kinase kinase Ste11 in wild-type cells leads to Cek1 activation and increased β (1,3)-glucan exposure. Thus, upregulation of the Cek1 MAPK pathway causes unmasking, and may be responsible for unmasking in cho1Δ/Δ."

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