Insights into the mode of action of anticandidal herbal monoterpenoid geraniol reveal disruption of multiple MDR mechani
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ORIGINAL PAPER
Insights into the mode of action of anticandidal herbal monoterpenoid geraniol reveal disruption of multiple MDR mechanisms and virulence attributes in Candida albicans Shweta Singh1 · Zeeshan Fatima1 · Saif Hameed1
Received: 21 November 2015 / Revised: 21 January 2016 / Accepted: 18 February 2016 © Springer-Verlag Berlin Heidelberg 2016
Abstract The anticandidal potential of Geraniol (Ger) against Candida albicans has already been established. The present study reveals deeper insights into the mechanisms of action of Ger. We observed that the repertoire of antifungal activity was not only limited to C. albicans and its clinical isolates but also against non-albicans species of Candida. The membrane tampering effect was visualized through transmission electron micrographs, depleted ergosterol levels and altered plasma membrane ATPase activity. Ger also affects cell wall as revealed by spot assays with cell wall-perturbing agents and scanning electron micrographs. Functional calcineurin pathway seems to be indispensable for the antifungal effect of Ger as calcineurin signaling mutant was hypersensitive to Ger while calcineurin overexpressing strain remained resistant. Ger also causes mitochondrial dysfunction, impaired iron homeostasis and genotoxicity. Furthermore, Ger inhibits both virulence attributes of hyphal morphogenesis and biofilm formation. Taken together, our results suggest that Ger is potential antifungal agent that warrants further investigation in clinical applications so that it could be competently employed in therapeutic strategies to treat Candida infections.
Communicated by Erko Stackebrandt. Shweta Singh and Zeeshan Fatima have contributed equally to this work. * Saif Hameed [email protected]; [email protected] 1
Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurgaon 122413, India
Keywords Candida · Geraniol · MDR · Calcineurin signaling · Cell wall · Cell membrane, biofilm
Introduction Candida albicans is an opportunistic human fungal pathogen which under wide ranges of immunocompromised conditions makes patients susceptible to superficial as well as systemic infections (Singh et al. 2015). The problem has become severe over the last decade considering the fact that Candida infections are fourth leading cause of mortality in patients infected with nosocomial infections (Wisplinghoff et al. 2004). Despite the availability of drugs for candidiasis such as azoles, polyenes, allylamines and echinocandins with distinct mode of actions, the persistent and prolonged use of these antibiotics resulted in the drug resistance which is termed as multidrug resistance (MDR) (Tanwar et al. 2014). Moreover, the collaborative effect of use of broad spectrum antibiotics, development of MDR and weakened immunity facilitates the Candida infections. Thus, there is constant need to find new and effective antifungals with novel targets. In the present scenario, given the limited number of effective antifungals, natural compounds from herbal origin can be a pr
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