Dr. Tulika Prasad, Assistant Professor, Jawaharlal Nehru University (JNU), New Delhi, India

Dr. Tulika Prasad is an Assistant Professor in Jawaharlal Nehru University (JNU), New Delhi, India. She is one of the founder faculty members of AIRF-JNU, a State of Art Research Laboratory. She works on Nanomedicine, Infectious Disease Biology and Multi Drug Resistance (MDR) especially in Candida albicans (a fungal pathogen) and Mycobacterium tuberculosis (Tuberculosis causing bacteria). She has a research group of 6 PhD students and two postdoctoral fellows.
Dr. Tulika has published around 42 original papers and book chapters in reputed peer-reviewed international journals and books. Her work has been awarded at several national and international conferences. She is recipient of i) Several Young Scientists Awards, ii) Ranbaxy Young Science Scholar Award for 2008 in the field of Medical Sciences by Ranbaxy Science Foundation and iii) Innovative Young Biotechnologist Award, 2008 by Department of Biotechnology, Govt. of India. She is Joint Secretary of the Nano Molecular Society, India.

Speech Title: Combating multidrug resistance (MDR) in pathogenic fungi, Candida: a nano-based approach

Aims: Nano-based antifungal therapeutic strategies for MDR reversal.

Methods: Spherical, stable 98% pure silver nanoparticles (AgNp) of average size 21.6 nm were prepared by chemical reduction which showed minimum inhibitory concentration (MIC90) at 40µgmL-1 for opportunistic fungal pathogen, Candida albicans. The AgNp augmented endogenous reactive oxygen species (ROS) and their significance in toxicity for Candida cells was investigated. The cellular targets involved in the mechanistic action of AgNp and synergistic potential of AgNp with 9 commonly used antifungal drugs of 6 different classes were evaluated against Candida cells.

Results: Use of AgNp among other metal nanoparticles has gained impetus for medical adoption because of its lower host toxicity. AgNp showed enhanced anti-Candidal activity when combined with different classes of antifungals at much lower concentration than their individual MICs. AgNp has been reported to induce oxidative stress mediated apoptosis through intracellular ROS accumulation. However, in this study, we found that AgNp augmented endogenous ROS production was completely inhibited by natural antioxidant (ascorbic acid). But restoration of basal levels of endogenous ROS by antioxidant could not completely reverse the AgNp induced sensitivity of fungal cells. It is possible that endogenous ROS either acts in parallel or in concerted action along with other cellular mechanisms. In addition to ROS generation, in our study, AgNp was found to affect other cellular targets resulting in altered membrane microenvironment, physical state of membrane, lipid composition, cellular ultrastructure and surface morphology. Thus, the multi-targeted action of AgNp, inhibition of drug efflux pump proteins, altered membrane fluidity and drug diffusion appears to potentiate synergism even at a sub-inhibitory concentration of AgNp and antifungals.

Conclusions: Our findings showed that ‘nanosilver-based drug combinations’ has the potential to address the challenges of multi-drug resistance (MDR) and fungal therapeutics by favoring broad spectrum activity, multiple cellular targets and minimal host toxicity.

Keywords: Silver Nanoparticles (AgNp), Candida albicans, Multidrug resistance, ergosterol