AiM  Vol.7 No.11 , November 2017
Phenazine Methosulphate Modulating the Expression of Genes Involved in Yeast to Hyphal Form Signal Transduction in Candida albicans
Candida albicans has ability to switch from yeast to hyphal form which is an important virulence factor. The objective of the research is to study the effect of Phenazine Methosulphate (PMS) on virulence factors and to study expression profile in yeast to hyphal form transition in C. albicans. Phenazine Methosulphate (PMS) acted as an inhibitor of yeast to hyphal form transition, adhesion and biofilm formation in C. albicans. RTPCR study demonstrated that PMS Modulate the expression of genes involved in Ras1-cAMP-Efg1 and Cek1-MAPK signal transduction pathways. Cell cycle of C. albicans was arrested at S phase on treatment of PMS. Hyphal suppressor genes like Tup1, Mig1 and Nrg1 were upregulated by PMS. Based on our data on expression of genes during yeast to hyphal form transition in presence and absence of PMS, we hypothesize that inhibition of hyphal formation may be due to the overexpression of negative regulators of hyphal growth. Targeting of hyphal specific genes involved in these pathways may be a promising strategy for anti-candida drug development.
Cite this paper: Jadhav, A. , Jangid, P. , Patil, R. , Gade, W. , Kharat, K. and Karuppayil, S. (2017) Phenazine Methosulphate Modulating the Expression of Genes Involved in Yeast to Hyphal Form Signal Transduction in Candida albicans. Advances in Microbiology, 7, 707-718. doi: 10.4236/aim.2017.711056.

[1]   Calderone, R.A. and Fonzi, W.A. (2001) Virulence Factors of Candida albicans. Current Trends in Microbiology, 9, 327-335.

[2]   Kumamoto, C.A. and Vinces, M.D. (2005) Contributions of Hyphae and Hypha-Co-Regulated Genes to Candida albicans Virulence. Cellular Microbiology, 7, 1546-1554.

[3]   Biswas S., Van Dijck P. and Datta, A. (2007) Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans. Microbiology and Molecular Biology Reviews, 71, 348-376.

[4]   Braun, B.R., Kadosh, D. and Johnson, A.D. (2001) NRG1, a Repressor of Filamentous Growth in C. albicans, is Down-Regulated during Filament Induction. EMBO Journal, 20, 4753-4761.

[5]   Carlisle, P.L., Banerjee, M., Lazzell, A., Monteagudo, C., López-Ribot, J.L. and Kadosh, D (2009) Expression Levels of a Filament-Specific Transcriptional Regulator Are Sufficient to Determine Candida albicans Morphology and Virulence. Proceedings of the National Academy of Sciences, 106, 599-604.

[6]   Jacobsen, I.D., Wilson, D., Wächtler, B., Brunke, S., Naglik, J.R. and Hube, B. (2012) Candida albicans Dimorphism as a Therapeutic Target. Expert Review of Anti-Infective Therapy, 10, 85-93.

[7]   Morales, D.K. and Hogan, D.A. (2010) Candida albicans Interactions with Bacteria in the Context of Human Health and Disease. PLOS Pathogens, 6, 1-4.

[8]   Morales, D.K., Jacobs, N.J., Rajamani, S., Krishnamurthy, M., Cubillos-Ruiz, J.R. and Hogan, D.A. (2010) Antifungal Mechanisms by Which a Novel Pseudomonas aeruginosa Phenazine Toxin Kills Candida albicans in Biofilms. Molecular Microbiology, 78, 1379-1392.

[9]   Gibson, J., Sood, A. and Hogan, D.A. (2009) Pseudomonas aeruginosa-Candida albicans Interactions: Localization and Fungal Toxicity of a Phenazine Derivative. Applied and Environmental Microbiology, 75, 504-513.

[10]   Raut, J.S., Shinde, R.B., Chauhan, N.M. and Mohan Karuppayil, S. (2013) Terpenoids of Plant Origin Inhibit Morphogenesis, Adhesion, and Biofilm Formation by Candida albicans. Biofouling, 29, 87-96.

[11]   Routh, M.M., Raut, J.S. and Karuppayil, S.M. (2011) Dual Properties of Anticancer Agents: An Exploratory Study on the in Vitro Anti-Candida Properties of Thirty Drugs. Chemother, 57, 372-380.

[12]   Shinde, R.B., Raut, J.S. and Karuppayil, S.M. (2012) Biofilm Formation by Candida albicans on Various Prosthetic Materials and Its Fluconazole Sensitivity: A Kinetic Study. Mycoscience, 53, 220-226.

[13]   Rajput, S.B. and Karuppayil, S.M. (2013) β-Asarone, an Active Principle of Acorus calamus Rhizome, Inhibits Morphogenesis, Biofilm Formation and Ergosterol Biosynthesis in Candida albicans. Phytomedicine, 20, 139-142.

[14]   Zore, G.B., Thakre, A.D., Jadhav, S. and Karuppayil, S.M. (2011) Terpenoids Inhibit Candida albicans Growth by Affecting Membrane Integrity and Arrest of Cell Cycle. Phytomedicine, 18, 1181-1190.

[15]   Chang, W., Li, Y., Zhang, L., Cheng, A. and Lou, H. (2012) Retigeric Acid B Attenuates the Virulence of Candida albicans via Inhibiting Adenylyl Cyclase Activity Targeted by Enhanced Farnesol Production. PLoS ONE, 7, 1-10.

[16]   Tupe, S.G., Kulkarni, R.R., Shirazi, F., Sant, D., Joshi, S.P. and Deshpande, M.V. (2015) Possible Mechanism of Antifungal Phenazine-1-Carboxamide from Pseudomonas sp. against Dimorphic Fungi Benjaminiella poitrasii and Human Pathogen Candida albicans. Journal of Applied Microbiology, 118, 39-48.

[17]   Staab, J.F., Bradway, S.D., Fidel, P.L. and Sundstrom, P. (1999) Adhesive and Mammalian Transglutaminase Substrate Properties of Candida albicans Hwp1. Science, 283, 1535-1538.

[18]   Feng, Q., Summers, E., Guo, B. and Fink, G. (1999) Ras Signaling Is Required for Serum-Induced Hyphal Differentiation in Candida albicans. Journal of Bacteriology, 181, 6339-6346.

[19]   Nobile, C.J., Andes, D.R., Nett, J.E., Smith, F.J., Yue, F., Phan, Q.T., Edwards, J.E., Filler, S.G. and Mitchell, A.P. (2006) Critical Role of Bcr1-Dependent Adhesins in C. albicans Biofilm Formation in Vitro and in Vivo. PLOS Pathogens, 2, 636-649.

[20]   Csank, C., Schröppel, K., Leberer, E., Harcus, D., Mohamed, O., Meloche, S., Thomas, D.Y. and Whiteway, M. (1998) Roles of the Candida albicans Mitogen-Activated Protein Kinase Homolog, Cek1p, in Hyphal Development and Systemic Candidiasis. Infection and Immunity, 66, 2713-2721.

[21]   Köhler, J.R. and Fink, G.R. (1996) Candida albicans Strains Heterozygous and Homozygous for Mutations in Mitogen-Activated Protein Kinase Signaling Components Have Defects in Hyphal Development. Proceedings of the National Academy of Sciences, 93, 13223-13228.

[22]   Leberer, E., Harcus, D., Broadbent, I.D., Clark, K.L., Dignard, D., Ziegelbauer, K., Schmidt, A., Gow, N.A., Brown, A.J. and Thomas, D.Y. (1996) Signal Transduction through Homologs of the Ste20p and Ste7p Protein Kinases Can Trigger Hyphal Formation in the Pathogenic Fungus Candida albicans. Proceedings of the National Academy of Sciences, 93, 13217-13222.

[23]   Kadosh, D. and Johnson, A.D. (2005) Induction of the Candida albicans Filamentous Growth Program by Relief of Transcriptional Repression: A Genome-Wide Analysis. Molecular Biology of the Cell, 16, 2903-2912.

[24]   Murad, A.M., Leng, P., Straffon, M., Wishart, J., Macaskill, S., MacCallum, D., Schnell, N., Talibi, D., Marechal, D., Tekaia, F. and d’Enfert, C. (2001) NRG1 Represses Yeast-Hypha Morphogenesis and Hypha-Specific Gene Expression in Candida albicans. The EMBO Journal, 20, 4742-4752.