Researchers from the Wadhwani School of Data Science and AI (WSAI), IIT Madras, and the ICMR-National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH) have developed an approach to study the fungal pathogen Candida albicans (CAL).
The multidisciplinary study applied an integrated systems biology method by combining large-scale computational modelling with experimental validation. This approach was used to identify unknown critical metabolic vulnerabilities in C. albicans, which is the primary cause of systemic candidiasis. The condition is considered a global health concern with mortality rates of up to 63.6 per cent in severe cases.
The rise of drug-resistant strains and a lack of new antifungal drugs underline the need for new therapeutic options. Current drug discovery processes often rely on trial-and-error screening, which is time-consuming and inefficient for identifying novel targets.
The research was led by Prof. Karthik Raman, Centre for Integrative Biology and Systems medicinE (IBSE) at WSAI, IIT Madras, and Prof. Susan Thomas, ICMR-NIRRCH, Mumbai. The team used a data-driven methodology to pinpoint unknown metabolic vulnerabilities in C. albicans.
The findings were published in the peer-reviewed journal Cell Communication and Signaling. Co-authors included Shuvechha Chakraborty, Indumathi Palanikumar, Yash Gune and Susan Idicula-Thomas from ICMR-NIRRCH, and K. V. Venkatesh and Prof. Karthik Raman from IIT Bombay.
Prof. Karthik Raman, Faculty, IBSE, WSAI, IIT Madras, said, “This groundbreaking novel research is vital for diversifying and improving antifungal drugs to bypass resistance. Further it aims to improve patient survival, reduce mortality and lower treatment costs.”
He added, “Currently, we have validated the preliminary key findings in animal models, which further need to be validated to understand more detailed mechanistic studies. Next steps would include collaboration with clinical partners to investigate these insights on real-world patient samples and the industry to develop these findings into antifungal treatments. As a whole, the findings underline India’s growing strength in interdisciplinary research and its potential to contribute solutions.”
Corresponding Author and Principal Investigator Dr Susan Thomas said, “Unlike other studies, the one-of-a-kind integrated host-fungal metabolic model combined the CAL model iRV781 with the human metabolic model Recon3D. This allowed the researchers to:
- Simulate how CAL metabolism responds during a host infection
- Identify and reveal hidden metabolic vulnerabilities not evident in laboratory cultures
- Highlight the role of arginine metabolism in C. albicans pathogenicity
- Introduce ‘ALT1’, a special enzyme as a ‘metabolic bottleneck’ in C. albicans virulence. As ALT1-deleted, C. albicans showed infection in the in vitro and mouse-based studies.”
Candida albicans is a species of fungus (yeast) that lives in the human body as part of the normal microbiota. It is commonly found in the mouth, throat, gut, vagina, and on the skin without causing harm in healthy individuals. It can cause systemic candidiasis, a severe invasive infection that spreads into the bloodstream and internal organs.
The annual incidence of invasive candidiasis in India is approximately 470,000 or 34 per 100,000 population. Globally, around 1,565,000 people are estimated to have a Candida bloodstream infection or invasive candidiasis each year, with 995,000 deaths (63.6 per cent)
As India’s premier institute, IIT Madras continues to contribute to research in science, engineering, and healthcare. The findings highlight WSAI’s role in interdisciplinary work and its contribution to solutions for health challenges.