On December 26, 2025, Professor Wang Linqi from the Chinese Academy of Sciences delivered an academic lecture titled "Drug Resistance, Evolution and Prevention and Control of Pathogens Causing Malignant Fungal Infections" at Building A7, Shahe Garden, Lihu Campus, Shenzhen University. He was invited by Professor Xinchun Chen from the School of Basic Medical Sciences, Health Science Center, as the guest speaker for the 161st session of the Shenzhen Medical Forum.

Professor Wang Linqi focused his presentation on fungal meningitis, one of the most life-threatening fungal infections, with Cryptococcus neoformans identified as the leading pathogen. At present, amphotericin B is the only fungicidal drug available for treating cryptococcal meningitis, yet treatment failure and recurrent infections remain common, and the underlying mechanisms are not fully understood.

His team evaluated the effects of hundreds of host metabolites on the fungicidal activity of amphotericin B and found that cerebral glucose plays a key role in enabling C. neoformans to tolerate amphotericin B-induced killing. They further clarified the mechanism by which glucose induces drug resistance in C. neoformans. The team identified a key regulatory factor responsible for this tolerance and confirmed that its activity significantly reduces the efficacy of amphotericin B treatment and increases the risk of disease recurrence. Mechanistically, glucose promotes the translocation of this regulatory factor from the cytoplasm to the nucleus, where it enhances the synthesis of inositol phosphorylceramide. This molecule competes with amphotericin B for binding to ergosterol, its target on the fungal cell membrane, thereby blocking drug binding and inducing tolerance.

The team also highlighted aureobasidin A, an inhibitor of inositol phosphorylceramide synthase, which has demonstrated favorable host safety. When combined with amphotericin B, aureobasidin A significantly improved therapeutic outcomes in animal models of cryptococcal meningitis, achieving a 7-day cure rate superior to that of the currently recommended amphotericin B–flucytosine regimen.

A key unresolved question is how C. neoformans survives amphotericin B treatment in the glucose-depleted environment of the lungs. A clinical study conducted 20 years ago suggested that the pathogen may form dormant cell populations during pulmonary infection. To explore this, Professor Wang Linqi’s team identified Sps1 as a molecular marker of dormancy by analyzing highly heterogeneous cryptococcal cell populations. They found that cells with high Sps1 expression exhibited enhanced tolerance to amphotericin B. In collaboration with the China Hospital Invasive Fungal Surveillance Network (CHIF-NET), the team collected over 1,000 clinical isolates of C. neoformans over a 13-year period. From here, they developed new methods for drug resistance detection and antifungal strategy design, including a persister evaluation system based on computer vision recognition.

Brief introduction to the speaker

Professor Wang Linqi is Deputy Director of the Institute of Microbiology, Chinese Academy of Sciences, Director of the Laboratory of Mycology and Innovative Biotechnology, and a Core Distinguished Researcher of the Chinese Academy of Sciences. He is an F1000 Faculty Member and a recipient of the National Science Fund for Distinguished Young Scholars. He received an "Excellent" rating in the final evaluation of the Chinese Academy of Sciences’ Hundred Talents Program. He serves as Chief Scientist of a National Key R&D Program and has been supported by both the National High-Level Young Talents Program and the National Science Fund for Excellent Young Scholars. His academic appointments include Chair of the Professional Committee of Microbial Genetics (Genetics Society of China), Chair of the Professional Committee of Genetics and Molecular Biology (Mycological Society of China), Vice Chair of the Professional Committee of General Microbiology (Chinese Society for Microbiology), and membership on the academic committees of the Institute of Microbiology, Chinese Academy of Sciences, and the Beijing Key Laboratory of Mechanistic Research and Precision Diagnosis of Invasive Fungal Diseases. He also serves on the expert committee of CHIF-NET. He has recently published as independent or corresponding author in leading journals includingNature Microbiology (three papers),Cell Host & Microbe,Nature Communications,Innovation,Annual Review of Microbiology,Advanced Drug Delivery Reviews,eLife, andPLoS Genetics.