New approach to fight fungal infection that claims one million lives annually

Chennai: Researchers at Wadhwani School of Data Science and AI (WSAI), IIT-M, and the ICMR-National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH) have developed a new approach to fight Candida albicans (CAL), a fungus that causes life-threatening infections.The team used an integrated systems biology method, combining computer-based modelling with laboratory experiments, to study the fungus during infection. They created an integrated model of the human metabolic model Recon3D and the CAL fungal metabolic model iRV781 to simulate how the fungus behaves inside the body. This helped them identify weaknesses in fungal metabolism that standard lab cultures do not reveal.A key finding is the role of arginine metabolism, the process by which the amino acid L-arginine is made and broken down into biologically important molecules. The study showed that it was important in how the fungus causes disease. The team also identified an enzyme called ALT1 as a metabolic bottleneck in CAL virulence. When ALT1 was deleted, the fungus showed reduced infection ability in both cell-based and mouse model studies.Candida albicans normally lives harmlessly in the human mouth, throat, gut, vagina, and skin. In people with weak immunity, however, it can spread into the bloodstream and internal organs, causing systemic candidiasis. This infection kills up to 63.6% of patients in severe cases. India reports around 4.7lakh cases every year, while globally about 16lakh people are affected, leading to nearly 10lakh deaths. The rise of drug-resistant strains and the lack of new antifungal drugs highlight the urgent need for new therapeutic strategies. Current drug discovery methods often rely on trial-and-error screening, which is time-consuming and inefficient in identifying novel targets.The research, led by Prof Karthik Raman of IIT-M and Prof Susan Thomas of ICMR-NIRRCH, was published in ‘Cell Communication and Signaling'. Prof. Raman said the team validated preliminary findings in animal models. The next step is to collaborate with clinical partners to test insights on patient samples and work with industry to develop antifungal treatments.