Indian researchers pioneer unique systems biology approach against fungal pathogens

New Delhi: Wadhwani School of Data Science and AI (WSAI), IIT Madras and ICMR-National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH) researchers have developed a one-of-a-kind approach to fight fungal pathogen called ‘Candida albicans’ (CAL).

This multidisciplinary approach employed an integrated systems biology approach – combining large-scale computational modelling and experimental validation – to identify unknown critical metabolic vulnerabilities in C.albicans. It is the primary cause of Systemic Candidiasis, a major global health threat with a high mortality rate up to 63.6% in severe cases.

The rise of drug-resistant strains and lack of new antifungal drugs underline the urgent need for new therapeutic options. The current drug discovery methodologies often rely on traditional trial-and-error screening, a time-consuming and inefficient process 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. They shifted their focus to data-driven method combining large-scale computational modelling and experimental validation – to identify unknown critical metabolic vulnerabilities in C.albicans.

The findings were published in reputed peer-reviewed journal Cell Communication and Signaling (https://doi.org/10.1186/s12964-025-02306-9) in a paper co-authored by Shuvechha Chakraborty, Indumathi Palanikumar, Yash Gune and Susan Idicula-Thomas from ICMR-NIRRCH, K. V. Venkatesh, Prof. Karthik Raman from IIT Bombay.

Highlighting the importance of this research, 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.”

Elaborating on the next steps in this research and how this research can be taken to real-world applications, Prof. Karthik Raman 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.”

Further, 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 stimulate 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; and 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 normally 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 causes ‘Systemic candidiasis’, a severe, invasive fungal infection caused by Candida species (most often Candida albicans) that spread beyond the mouth, skin, or genital area into the bloodstream and internal organs.

The annual incidence of invasive candidiasis in India is ∼470 000 or 34/100 000 population (Ray et al., 2022 – https://doi.org/10.1093/ofid/ofac603). Globally, about 1 565 000 people have a Candida bloodstream infection or invasive candidiasis each year, with 995 000 deaths (63·6%) (Denning et al., 2024 – https://doi.org/10.1016/S1473-3099(23)00692-8)

As India’s premier institute, IIT Madras continues to contribute to science, engineering and healthcare innovations. The research findings highlight WSAI’s strength in interdisciplinary research and its contribution in providing solutions to global health challenges.