Frédéric Lamoth Lab

Frédéric Lamoth, Associate Professor and Senior Physician In the field of Medical Mycology
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Research Topic

Fungi, such as yeasts and molds, can cause invasive infections in humans, in particular among severely ill patients (admitted in intensive care units) or those with immune defects (e.g. cancer, transplantation). The yeasts of the genus Candida can cause bloodstream infections (candidemia), while the molds, such as Aspergillus or the Mucorales, cause lung infections or disseminated infections (invasive aspergillosis, mucormycosis). These invasive fungal infections are associated with high mortality rates.

Therapeutic options for invasive fungal infections are limited. Resistance to antifungal drugs is increasing among Candida and Aspergillus, while the Mucorales and other rare pathogenic molds are naturally resistant to many antifungal drugs.

Our laboratory investigates the mechanisms of resistance to antifungal drugs (in particular the azoles and the echinocandins) of three relevant pathogenic fungi: Candida auris, Aspergillus fumigatus and Mucor circinelloides.

Mechanisms of resistance in Aspergillus fumigatus and Mucor circinelloides

We have deciphered the role of the heat shock protein 90 (Hsp90) in the tolerance of Aspergillus fumigatus to the echinocandin drug caspofungin. We also investigate the mechanisms of resistance to azoles mediated by efflux pumps in Aspergillus fumigatus and Mucor circinelloides.

Mechanisms of resistance in Candida auris

Candida auris is an emerging pathogenic yeast causing nosocomial outbreaks. This fungus has the ability to develop resistance to multiple antifungal drugs. Our laboratory investigates the mechanisms of azole resistance in C. auris, such as those mediated via gain-of-function mutations in transcription factors and subsequent overexpression of efflux pumps.

Research funding

Swiss National Science Foundation

Santos-Suarez Foundation

Echinocandin Tolerance and Paradoxal Effect

Aspergillus fumigatus exhibits some level of natural resistance to echinocandin drugs (e.g. caspofungin) with loss of efficacy at high drug concentrations (paradoxical effect). We investigate the network and intracellular pathways mediated by the heat shock proteins (Hsp90 and Hsp70) in this response.

Acquired Resistance to Triazoles

Triazoles (e.g. voriconazole) represent the first-line treatment of invasive aspergillosis. Emergence of resistance due to well-defined mutations of the target gene (cyp51a) has been described. However, there are other mechanisms of stress adaptation which may be involved in the resistance to triazoles. We analyze the impact of prolonged triazole exposure of A. fumigatus strains on the development of resistance mediated by activation of efflux transporters.

Fundings

  • Swiss National Science Foundation (Ambizione-Score)
  • Santos-Suarez Foundation
 Last updated on 27/02/2023 at 15:20