ICMR, IIT-M, Wadhwani develop novel way against Candida, a lethal fungal pathogen

Chennai: Researchers at the Wadhwani School of Data Science and AI (WSAI), IIT Madras, and the Indian Council of Medical Research (ICMR) have developed a groundbreaking systems biology approach to combat Candida albicans (CAL), a lethal fungal pathogen.

This innovative, data-driven methodology could pave the way for a new generation of antifungal drugs, helping to bypass drug resistance, improve patient survival and reduce mortality rates and treatment costs.

Integrated host-fungal model yields breakthrough

The research, led by Prof Karthik Raman (IIT Madras) and Prof Susan Thomas (ICMR-NIRRCH, Mumbai), moved away from traditional, inefficient trial-and-error drug discovery.

They created a unique integrated host-fungal metabolic model by combining the CAL model iRV781 with the human metabolic model Recon3D. This allowed them to simulate the pathogen’s behaviour during a host infection, identifying hidden metabolic vulnerabilities that aren’t visible in lab cultures.

Metabolic bottleneck

A key finding was the role of arginine metabolism in CAL’s pathogenicity.

The researchers pinpointed a specific enzyme, ALT1, as a ‘metabolic bottleneck’ in the pathogen’s ability to cause disease.

By targeting this enzyme, they can disrupt the fungus’s virulence. Experimental validation in both in vitro and mouse-based studies confirmed that deleting the ALT1 enzyme significantly impaired the fungus’s ability to infect.

Global health threat and impact on India

* C albicans is a major global health threat, responsible for Systemic Candidiasis, a severe invasive infection with a mortality rate as high as 63.6 per cent in severe cases.

* The rise of drug-resistant strains has made the development of new treatments a matter of urgent public health concern.

* 1.56 million people globally suffer from Candida bloodstream infections

* According to a 2024 study by Denning et al., approximately 1.56 million people worldwide suffer from Candida bloodstream infections or invasive candidiasis annually, resulting in around 995,000 deaths.

* The annual incidence of invasive candidiasis in India is estimated to be approximately 470,000 cases, or 34 cases per 100,000 people, as per a 2022 study by Ray et al.

Potential for lowered treatment costs

While specific treatment costs vary widely based on the severity of the infection and type of drug used, invasive candidiasis requires hospitalisation and expensive antifungal medications like echinocandins, which can be prohibitively expensive, especially in developing countries like India.