Alexandre Alanio, a reference in medical mycology, gave a lecture at the Institut Pasteur de São Paulo, describing how the dormancy and persistence of Cryptococcus neoformans affect public health and pose challenges for medicine.
Invasive fungal infections, such as cryptococcosis, continue to be a worldwide public health problem, especially in immunocompromised patients. With high mortality rates, these infections can remain dormant in the body for years before reactivating, defying conventional diagnoses and treatments. This was the central concern of a lecture given on May 26 by researcher Alexandre Alanio, an international reference in the study of pathogenic fungi, at the Institut Pasteur de São Paulo.
A Professor at the University Paris Cité (Hospital Saint Louis, Paris, France) and head of the translational mycology group and deputy director of the National Reference Center for Mycoses and Antifungals in France, Alexandre Alanio also teaches the Medical Mycology course at the Institut Pasteur de Paris. At the seminar, he shared findings that show how Cryptococcus neoformans can “hide” in the body in states called dormancy and persistence. These states prevent the fungus, even when alive, from being detected or effectively combated, increasing the risk of late complications.
According to Prof. Alanio, dormant cells, described as viable but non culturable cells, can hide in the body for years, sheltered in organs such as the lungs or in macrophages (the body’s defense cells), before reactivating when the patient’s immunity weakens. On the other hand, the so-called persistent cells, can survive even under powerful treatments, such as Amphotericin B, without developing definitive genetic resistance. “These persistent cells have a reduced metabolism and are able to temporarily tolerate the stress caused by antifungal drugs,” he said. These findings help us understand why, in some patients, the disease returns even after long treatments.
He presented experiments that simulate these conditions in the laboratory, revealing how the fungus adapts to survive in hostile environments. “For example, reduced oxygen and nutrients causes some of the cells to become viable, but unable to grow in culture – which defies conventional Pasteurian microbiology .” Alanio also explained that, in macrophages, dormant cells remain practically inert, but can reactivate and proliferate again when released through processes such as nonlytic exocytosis, a finding that reinforces the importance of understanding the interaction between the fungus and the body’s defense cells. He also highlighted the role of extracellular vesicles and molecules such as pantothenic acid, which were shown to stimulate the reactivation of dormant cells.
New paths for diagnosis and treatment
In addition to explaining these mechanisms, Alanio shared important clues that may pave the way for new approaches to diagnosis and treatment. One of these is the use of molecular tests to detect the expression of specific genes, such as QSP1, which indicates the presence of live fungal cells even when they cannot be cultivated in the laboratory – an essential step in monitoring patients with cryptococcosis.
He also highlighted that molecules such as pantothenic acid and extracellular vesicles can reactivate dormant cells, indicating potential therapeutic targets. He reported that these vesicles carry nutrients and molecular signals that help reactivate dormant cells, a mechanism that can be explored for future therapeutic strategies. At last, he emphasized that the combined use of antifungals, such as Amphotericin B with 5-FC, is more effective than monotherapy in eradicating persistent fungus populations – an essential information for improving clinical protocols and reducing relapses.