Abstract

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.

Highlights

  • Yeast to Hyphal (Y-H) form morphogenesis is one of the major virulence factors in C. albicans and this may facilitate penetration of epithelial tissues and escape from host immune response [1] [2]

  • More than 90% (p < 0.05) of the growth was inhibited at 0.062 mg/ml. 99% of planktonic growth was inhibited by Phenazine Methosulphate (PMS) after 48 hrs of exposure at 0.25 mg/ml (Table 1)

  • Our in vitro study revealed that PMS inhibited major virulence factors in C. albicans like morphogenesis and adhesion. qPCR studies showed that PMS affects the signal transduction pathways in yeast to hyphal transition in C. albicans

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Summary

Introduction

Yeast to Hyphal (Y-H) form morphogenesis is one of the major virulence factors in C. albicans and this may facilitate penetration of epithelial tissues and escape from host immune response [1] [2]. Upregulation of hyphal specific genes are reported during yeast to hyphal form transformation [5]. Targeting of hyphal specific genes involved in these pathways may be a promising strategy for anti-Candida drug development [6]. In this study the effect of Phenazine methosulphate (PMS) on the expression of genes involved in Yeast to hyphal transition is explored

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