Christophe D’Enfert

Website: https://research.pasteur.fr/en/team/fungal-biology-and-pathogenicity/
ORCID: 0000-0002-6235-3886

In the recent years, fungal infections have become a prominent problem. This in part reflects the increase in immunocompromized individuals (HIV infected individuals, transplant recipients, patients in intensive care units) as well as increased life expectancy. In developed countries, fungal infections are considered as one of the primary causes of nosocomial infections. Hemiascomycetous yeasts of the genus Candida, and most notably Candida albicans, are responsible for most of the life-threatening systemic fungal infections, especially among intensive-care unit (ICU) patients, cancer patients receiving chemotherapy and patients awaiting transplantation. Life-threatening infections due to Candida species are estimated at > 400,000 cases and ~200,000 deaths per year and represent a real concern because of their high mortality rate, despite the availability of antifungal treatments and other therapeutic approaches.

In this context, The Fungal Biology and Pathogenicity Unit at Institut Pasteur studies at the molecular level several processes contributing to the pathogenicity of Candida albicans:

– genome plasticity and its role in adapting to the different contexts encountered in the host;

– colonization of abiotic and biotic surfaces and the formation of antifungal-tolerant biofilms;

– morphological transitions, such as the alternation between yeast and filamentous forms that play an important role during infection;

– cell wall biogenesis, the understanding of which should lead to new antifungal strategies;

– interaction with the gut microbiota.

This work is based on the study of the natural genetic diversity of C. albicans, with a large collection of genome-sequenced isolates, and on functional genomics tools developed in the unit (eg the C. albicans ORFeome).

The unit is also developing a program to identify antifungal molecules targeting enzymes that regulate adaptive responses in Candida glabrata and the emerging pathogen Candida auris.

Top 5 publications

1. Marton T, Chauvel M, Feri A, Maufrais C, D’enfert C, Legrand M. Factors that influence bidirectional long-tract homozygosis due to double-strand break repair in Candida albicans. Genetics. 2021; 218:iyab028.
2. Hernández-Cervantes A, Znaidi S, van Wijlick L, Denega I, Basso V, Ropars J, Sertour N, Sullivan D, Moran G, Basmaciyan L, Bon F, Dalle F, Bougnoux ME, Boekhout T, Yang Y, Li Z, Bachellier-Bassi S, d’Enfert C. A conserved regulator controls asexual sporulation in the fungal pathogen Candida albicans. Nat Commun. 2020; 11:6224.
3. Sitterlé E, Coste AT, Obadia T, Maufrais C, Chauvel M, Sertour N, Sanglard D, Puel A, D’Enfert C, Bougnoux ME. Large-scale genome mining allows identification of neutral polymorphisms and novel resistance mutations in genes involved in Candida albicans resistance to azoles and echinocandins. J Antimicrob Chemother. 2020; 75:835-848.
4. Znaidi S, van Wijlick L, Hernández-Cervantes A, Sertour N, Desseyn JL, Vincent F, Atanassova R, Gouyer V, Munro CA, Bachellier-Bassi S, Dalle F, Jouault T, Bougnoux ME, d’Enfert C. Systematic gene overexpression in Candida albicans identifies a regulator of early adaptation to the mammalian gut. Cell Microbiol. 2018; 20:e12890.
5. Legrand M, Bachellier-Bassi S, Lee KK, Chaudhari Y, Tournu H, Arbogast L, Boyer H, Chauvel M, Cabral V, Maufrais C, Nesseir A, Maslanka I, Permal E, Rossignol T, Walker LA, Zeidler U, Znaidi S, Schoeters F, Majgier C, Julien RA, Ma L, Tichit M, Bouchier C, Van Dijck P, Munro CA, d’Enfert C. Generating genomic platforms to study Candida albicans pathogenesis. Nucleic Acids Res. 2018; 46:6935-6949.
6. Ropars J, Maufrais C, Diogo D, Marcet-Houben M, Perin A, Sertour N, Mosca K, Permal E, Laval G, Bouchier C, Ma L, Schwartz K, Voelz K, May RC, Poulain J, Battail C, Wincker P, Borman AM, Chowdhary A, Fan S, Kim SH, Le Pape P, Romeo O, Shin JH, Gabaldon T, Sherlock G, Bougnoux ME, d’Enfert C. Gene flow contributes to diversification of the major fungal pathogen Candida albicans. Nat Commun. 2018; 9:2253.

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