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1. Secretion of the fungal toxin candidalysin is dependent on conserved precursor peptide sequences

Author

Müller, Rita, König, Annika, Groth, Sabrina, Zarnowski, Robert, Visser, Corissa, Handrianz, Tom, Maufrais, Corinne, Krüger, Thomas, Himmel, Maximilian, Lee, Sejeong, Priest, Emily L., Yildirim, Deniz, Richardson, Jonathan P., Blango, Matthew G., Bougnoux, Marie-Elisabeth, Kniemeyer, Olaf, d’Enfert, Christophe, Brakhage, Axel A., Andes, David R., Trümper, Verena, Nehls, Christian, Kasper, Lydia, Mogavero, Selene, Gutsmann, Thomas, Naglik, Julian R., Allert, Stefanie, and Hube, Bernhard

Published
2024
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7. Integrated analysis of whole blood oxylipin and cytokine responses after bacterial, viral, and T cell stimulation reveals new immune networks

Author

Abel, Laurent, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Bourke, Nollaig, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’Enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Eberl, Gérard, Enninga, Jost, Fellay, Jacques, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly A., Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Mouquet, Hugo, O'Farrelly, Cliona, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew L., Duffy, Darragh, Quintana-Murci, Lluis, Villain, Etienne, Chanson, Aurélie, Mainka, Malwina, Kampschulte, Nadja, Le Faouder, Pauline, Bertrand-Michel, Justine, Brandolini-Bunlon, Marion, Charbit, Bruno, Musvosvi, Munyaradzi, Bilek, Nicole, Scriba, Thomas J., Schebb, Nils Helge, and Gladine, Cécile

Published
2023
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8. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.

Author

Gordon, David E, Jang, Gwendolyn M, Bouhaddou, Mehdi, Xu, Jiewei, Obernier, Kirsten, O'Meara, Matthew J, Guo, Jeffrey Z, Swaney, Danielle L, Tummino, Tia A, Hüttenhain, Ruth, Kaake, Robyn M, Richards, Alicia L, Tutuncuoglu, Beril, Foussard, Helene, Batra, Jyoti, Haas, Kelsey, Modak, Maya, Kim, Minkyu, Haas, Paige, Polacco, Benjamin J, Braberg, Hannes, Fabius, Jacqueline M, Eckhardt, Manon, Soucheray, Margaret, Bennett, Melanie J, Cakir, Merve, McGregor, Michael J, Li, Qiongyu, Naing, Zun Zar Chi, Zhou, Yuan, Peng, Shiming, Kirby, Ilsa T, Melnyk, James E, Chorba, John S, Lou, Kevin, Dai, Shizhong A, Shen, Wenqi, Shi, Ying, Zhang, Ziyang, Barrio-Hernandez, Inigo, Memon, Danish, Hernandez-Armenta, Claudia, Mathy, Christopher JP, Perica, Tina, Pilla, Kala B, Ganesan, Sai J, Saltzberg, Daniel J, Ramachandran, Rakesh, Liu, Xi, Rosenthal, Sara B, Calviello, Lorenzo, Venkataramanan, Srivats, Lin, Yizhu, Wankowicz, Stephanie A, Bohn, Markus, Trenker, Raphael, Young, Janet M, Cavero, Devin, Hiatt, Joe, Roth, Theo, Rathore, Ujjwal, Subramanian, Advait, Noack, Julia, Hubert, Mathieu, Roesch, Ferdinand, Vallet, Thomas, Meyer, Björn, White, Kris M, Miorin, Lisa, Agard, David, Emerman, Michael, Ruggero, Davide, García-Sastre, Adolfo, Jura, Natalia, von Zastrow, Mark, Taunton, Jack, Schwartz, Olivier, Vignuzzi, Marco, d'Enfert, Christophe, Mukherjee, Shaeri, Jacobson, Matt, Malik, Harmit S, Fujimori, Danica G, Ideker, Trey, Craik, Charles S, Floor, Stephen, Fraser, James S, Gross, John, Sali, Andrej, Kortemme, Tanja, Beltrao, Pedro, Shokat, Kevan, Shoichet, Brian K, and Krogan, Nevan J

Subjects
Prevention, Vaccine Related, Biodefense, Infectious Diseases, Rare Diseases, Pneumonia & Influenza, Emerging Infectious Diseases, Lung, Pneumonia, 5.1 Pharmaceuticals, 2.2 Factors relating to the physical environment, Infection
Abstract

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

Published
2020

12. A gain-of-function mutation in zinc cluster transcription factor Rob1 Drives Candida albicans adaptive growth in the cystic fibrosis lung environment

Author

Gnaien, Mayssa, primary, Maufrais, Corinne, additional, Rebai, Yasmine, additional, Kallel, Aicha, additional, Ma, Laurence, additional, Hamouda, Samia, additional, Khalsi, Fatma, additional, Meftah, Khaoula, additional, Smaoui, Hanen, additional, Khemiri, Monia, additional, Hadj Fredj, Sondes, additional, Bachellier-Bassi, Sophie, additional, Najjar, Imène, additional, Messaoud, Taieb, additional, Boussetta, Khadija, additional, Kallel, Kalthoum, additional, Mardassi, Helmi, additional, d’Enfert, Christophe, additional, Bougnoux, Marie-Elisabeth, additional, and Znaidi, Sadri, additional

Published
2024
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14. Impact of socioeconomic status on healthy immune responses in humans.

Author

Bertrand, Anthony, Sugrue, Jamie, Lou, Tianai, Bourke, Nollaig M, Quintana‐Murci, Lluis, Saint‐André, Violaine, O'Farrelly, Cliona, Duffy, Darragh, Abel, Laurent, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Bourke, Nollaig, Brodin, Petter, Bruhns, Pierre, Cerf‐Bensussan, Nadine, Cumano, Ana, D'Enfert, Christophe, Demangel, Caroline, and Deriano, Ludovic

Subjects
HOME ownership, RANDOM forest algorithms, SOCIOECONOMIC status, IMMUNE response, GENETICS
Abstract

Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared with people with higher SES. Age, sex, host genetics, smoking and cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo‐rating system using socioeconomic features such as education, income and home ownership status to objectively rank SES in the 1000 donors. We observed sex‐specific SES associations, such as females with a low SES having a significantly higher frequency of CMV seropositivity compared with females with high SES, and males with a low SES having a significantly higher frequency of active smoking compared with males with a high SES. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES‐dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind SES effects on immune responses and ultimately disease. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Methodologies for in vitro and in vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms.

Author

Van Dijck, Patrick, Sjollema, Jelmer, Cammue, Bruno P, Lagrou, Katrien, Berman, Judith, d'Enfert, Christophe, Andes, David R, Arendrup, Maiken C, Brakhage, Axel A, Calderone, Richard, Cantón, Emilia, Coenye, Tom, Cos, Paul, Cowen, Leah E, Edgerton, Mira, Espinel-Ingroff, Ana, Filler, Scott G, Ghannoum, Mahmoud, Gow, Neil AR, Haas, Hubertus, Jabra-Rizk, Mary Ann, Johnson, Elizabeth M, Lockhart, Shawn R, Lopez-Ribot, Jose L, Maertens, Johan, Munro, Carol A, Nett, Jeniel E, Nobile, Clarissa J, Pfaller, Michael A, Ramage, Gordon, Sanglard, Dominique, Sanguinetti, Maurizio, Spriet, Isabel, Verweij, Paul E, Warris, Adilia, Wauters, Joost, Yeaman, Michael R, Zaat, Sebastian AJ, and Thevissen, Karin

Subjects
antibiofilm material coating, antifungal susceptibility testing, biofilm eradication, biofilm inhibition, in vivo models
Abstract

Unlike superficial fungal infections of the skin and nails, which are the most common fungal diseases in humans, invasive fungal infections carry high morbidity and mortality, particularly those associated with biofilm formation on indwelling medical devices. Therapeutic management of these complex diseases is often complicated by the rise in resistance to the commonly used antifungal agents. Therefore, the availability of accurate susceptibility testing methods for determining antifungal resistance, as well as discovery of novel antifungal and antibiofilm agents, are key priorities in medical mycology research. To direct advancements in this field, here we present an overview of the methods currently available for determining (i) the susceptibility or resistance of fungal isolates or biofilms to antifungal or antibiofilm compounds and compound combinations; (ii) the in vivo efficacy of antifungal and antibiofilm compounds and compound combinations; and (iii) the in vitro and in vivo performance of anti-infective coatings and materials to prevent fungal biofilm-based infections.

Published
2018

17. A CO 2 sensing module modulates β-1,3-glucan exposure in Candida albicans

Author

Avelar, Gabriela M., primary, Pradhan, Arnab, additional, Ma, Qinxi, additional, Hickey, Emer, additional, Leaves, Ian, additional, Liddle, Corin, additional, Rodriguez Rondon, Alejandra V., additional, Kaune, Ann-Kristin, additional, Shaw, Sophie, additional, Maufrais, Corinne, additional, Sertour, Natacha, additional, Bain, Judith M., additional, Larcombe, Daniel E., additional, de Assis, Leandro J., additional, Netea, Mihai G., additional, Munro, Carol A., additional, Childers, Delma S., additional, Erwig, Lars P., additional, Brown, Gordon D., additional, Gow, Neil A. R., additional, Bougnoux, Marie-Elisabeth, additional, d'Enfert, Christophe, additional, and Brown, Alistair J. P., additional

Published
2024
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20. Metabolic reprogramming during Candida albicans planktonic-biofilm transition is modulated by the transcription factors Zcf15 and Zcf26.

Author

Rai, Laxmi Shanker, Chauvel, Murielle, Sanchez, Hiram, van Wijlick, Lasse, Maufrais, Corinne, Cokelaer, Thomas, Sertour, Natacha, Legrand, Mélanie, Sanyal, Kaustuv, Andes, David R., Bachellier-Bassi, Sophie, and d'Enfert, Christophe

Subjects
CANDIDA albicans, METABOLIC reprogramming, TRANSCRIPTION factors, KREBS cycle, ARTIFICIAL implants, HUMAN microbiota
Abstract

Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulating C. albicans biofilm formation, we performed a large-scale screen with 2,454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their role in reprogramming cellular metabolism by regulating central metabolism including glyoxylate and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling. Fungal biofilms are complex communities that can form on surfaces of implanted medical devices. This study uses an overexpression screen to identify novel modulators of Candida albicans biofilm formation, revealing that the transcription factors ZCF15 and ZCF26 regulate metabolic reprogramming during the transition from planktonic to biofilm growth. [ABSTRACT FROM AUTHOR]

Published
2024
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21. From Genes to Networks: The Regulatory Circuitry Controlling Candida albicans Morphogenesis

Author

Basso, Virginia, d’Enfert, Christophe, Znaidi, Sadri, Bachellier-Bassi, Sophie, Ahmed, Rafi, Series Editor, Akira, Shizuo, Series Editor, Aktories, Klaus, Series Editor, Casadevall, Arturo, Series Editor, Compans, Richard W, Series Editor, Galan, Jorge E, Series Editor, Garcia-Sastre, Adolfo, Series Editor, Malissen, Bernard, Series Editor, Rappuoli, Rino, Series Editor, and Rodrigues, Marcio L., editor

Published
2019
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23. Unveiling Candida albicans intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response

Author

Delavy, Margot, primary, Sertour, Natacha, additional, Patin, Etienne, additional, Le Chatelier, Emmanuelle, additional, Cole, Nathaniel, additional, Dubois, Florian, additional, Xie, Zixuan, additional, Saint-André, Violaine, additional, Manichanh, Chaysavanh, additional, Walker, Alan W., additional, Quintana-Murci, Lluis, additional, Duffy, Darragh, additional, d’Enfert, Christophe, additional, Bougnoux, Marie-Elisabeth, additional, and Consortium, Milieu Intérieur, additional

Published
2023
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25. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

Author

Gordon, David E., Jang, Gwendolyn M., Bouhaddou, Mehdi, Xu, Jiewei, Obernier, Kirsten, White, Kris M., O’Meara, Matthew J., Rezelj, Veronica V., Guo, Jeffrey Z., Swaney, Danielle L., Tummino, Tia A., Hüttenhain, Ruth, Kaake, Robyn M., Richards, Alicia L., Tutuncuoglu, Beril, Foussard, Helene, Batra, Jyoti, Haas, Kelsey, Modak, Maya, Kim, Minkyu, Haas, Paige, Polacco, Benjamin J., Braberg, Hannes, Fabius, Jacqueline M., Eckhardt, Manon, Soucheray, Margaret, Bennett, Melanie J., Cakir, Merve, McGregor, Michael J., Li, Qiongyu, Meyer, Bjoern, Roesch, Ferdinand, Vallet, Thomas, Mac Kain, Alice, Miorin, Lisa, Moreno, Elena, Naing, Zun Zar Chi, Zhou, Yuan, Peng, Shiming, Shi, Ying, Zhang, Ziyang, Shen, Wenqi, Kirby, Ilsa T., Melnyk, James E., Chorba, John S., Lou, Kevin, Dai, Shizhong A., Barrio-Hernandez, Inigo, Memon, Danish, Hernandez-Armenta, Claudia, Lyu, Jiankun, Mathy, Christopher J. P., Perica, Tina, Pilla, Kala Bharath, Ganesan, Sai J., Saltzberg, Daniel J., Rakesh, Ramachandran, Liu, Xi, Rosenthal, Sara B., Calviello, Lorenzo, Venkataramanan, Srivats, Liboy-Lugo, Jose, Lin, Yizhu, Huang, Xi-Ping, Liu, YongFeng, Wankowicz, Stephanie A., Bohn, Markus, Safari, Maliheh, Ugur, Fatima S., Koh, Cassandra, Savar, Nastaran Sadat, Tran, Quang Dinh, Shengjuler, Djoshkun, Fletcher, Sabrina J., O’Neal, Michael C., Cai, Yiming, Chang, Jason C. J., Broadhurst, David J., Klippsten, Saker, Sharp, Phillip P., Wenzell, Nicole A., Kuzuoglu-Ozturk, Duygu, Wang, Hao-Yuan, Trenker, Raphael, Young, Janet M., Cavero, Devin A., Hiatt, Joseph, Roth, Theodore L., Rathore, Ujjwal, Subramanian, Advait, Noack, Julia, Hubert, Mathieu, Stroud, Robert M., Frankel, Alan D., Rosenberg, Oren S., Verba, Kliment A., Agard, David A., Ott, Melanie, Emerman, Michael, Jura, Natalia, von Zastrow, Mark, Verdin, Eric, Ashworth, Alan, Schwartz, Olivier, d’Enfert, Christophe, Mukherjee, Shaeri, Jacobson, Matt, Malik, Harmit S., Fujimori, Danica G., Ideker, Trey, Craik, Charles S., Floor, Stephen N., Fraser, James S., Gross, John D., Sali, Andrej, Roth, Bryan L., Ruggero, Davide, Taunton, Jack, Kortemme, Tanja, Beltrao, Pedro, Vignuzzi, Marco, García-Sastre, Adolfo, Shokat, Kevan M., Shoichet, Brian K., and Krogan, Nevan J.

Published
2020
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27. The pathogenic and colonization potential of Candida africana

Author

Kosmala, Daria, primary, Sertour, Natacha, additional, Fróis Martins, Ricardo, additional, Spaggiari, Luca, additional, Ardizzoni, Andrea, additional, LeibundGut-Landmann, Salomé, additional, Pericolini, Eva, additional, Bougnoux, Marie-Elisabeth, additional, d’Enfert, Christophe, additional, and Legrand, Mélanie, additional

Published
2023
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28. Metabolic reprogramming duringCandida albicansplanktonic-biofilm transition is modulated by theZCF15andZCF26paralogs

Author

Rai, Laxmi Shanker, primary, Chauvel, Murielle, additional, Sanchez, Hiram, additional, van Wijlick, Lasse, additional, Maufrais, Corinne, additional, Cokelaer, Thomas, additional, Sertour, Natacha, additional, Legrand, Mélanie, additional, Andes, David R, additional, Bachellier-Bassi, Sophie, additional, and d’Enfert, Christophe, additional

Published
2023
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29. Genome Diversity and Dynamics in Candida albicans

Author

d’Enfert, Christophe, Bougnoux, Marie-Elisabeth, Feri, Adeline, Legrand, Mélanie, Loll-Krippleber, Raphaël, Marton, Timea, Maufrais, Corinne, Ropars, Jeanne, Sertour, Natacha, Sitterlé, Emilie, and Prasad, Rajendra, editor

Published
2017
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31. Comparing genomic variant identification protocols for Candida auris

Author

Li, Xiao, primary, Muñoz, José F., additional, Gade, Lalitha, additional, Argimon, Silvia, additional, Bougnoux, Marie-Elisabeth, additional, Bowers, Jolene R., additional, Chow, Nancy A., additional, Cuesta, Isabel, additional, Farrer, Rhys A., additional, Maufrais, Corinne, additional, Monroy-Nieto, Juan, additional, Pradhan, Dibyabhaba, additional, Uehling, Jessie, additional, Vu, Duong, additional, Yeats, Corin A., additional, Aanensen, David M., additional, d’Enfert, Christophe, additional, Engelthaler, David M., additional, Eyre, David W., additional, Fisher, Matthew C., additional, Hagen, Ferry, additional, Meyer, Wieland, additional, Singh, Gagandeep, additional, Alastruey-Izquierdo, Ana, additional, Litvintseva, Anastasia P., additional, and Cuomo, Christina A., additional

Published
2023
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32. Candida albicans Adhesion Measured by Optical Nanomotion Detection.

Author

Villalba, Maria I., LeibundGut-Landmann, Salomé, Bougnoux, Marie-Elisabeth, d'Enfert, Christophe, Willaert, Ronnie G., and Kasas, Sandor

Subjects
CANDIDA albicans, CELL motility, MICROSCOPY, DIGITAL image correlation
Abstract

Cellular adhesion plays an important role in numerous fundamental physiological and pathological processes. Its measurement is relatively complex, requires sophisticated equipment, and, in most cases, cannot be carried out without breaking the links between the studied cell and its target. In this contribution, we propose a novel, nanomotion-based, technique that overcomes these drawbacks. The applied force is generated by the studied cell itself (nanomotion), whereas cellular movements are detected by traditional optical microscopy and dedicated software. The measurement is non-destructive, single-cell sensitive, and permits following the evolution of the adhesion as a function of time. We applied the technique on different strains of the fungal pathogen Candida albicans on a fibronectin-coated surface. We demonstrated that this novel approach can significantly simplify, accelerate, and make more affordable living cells–substrate adhesion measurements. [ABSTRACT FROM AUTHOR]

Published
2023
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33. A human-curated annotation of the Candida albicans genome.

Author

Braun, Burkhard R, van Het Hoog, Marco, d'Enfert, Christophe, Martchenko, Mikhail, Dungan, Jan, Kuo, Alan, Inglis, Diane O, Uhl, M Andrew, Hogues, Hervé, Berriman, Matthew, Lorenz, Michael, Levitin, Anastasia, Oberholzer, Ursula, Bachewich, Catherine, Harcus, Doreen, Marcil, Anne, Dignard, Daniel, Iouk, Tatiana, Zito, Rosa, Frangeul, Lionel, Tekaia, Fredj, Rutherford, Kim, Wang, Edwin, Munro, Carol A, Bates, Steve, Gow, Neil A, Hoyer, Lois L, Köhler, Gerwald, Morschhäuser, Joachim, Newport, George, Znaidi, Sadri, Raymond, Martine, Turcotte, Bernard, Sherlock, Gavin, Costanzo, Maria, Ihmels, Jan, Berman, Judith, Sanglard, Dominique, Agabian, Nina, Mitchell, Aaron P, Johnson, Alexander D, Whiteway, Malcolm, and Nantel, André

Subjects
Genetics, Developmental Biology
Abstract

Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications.

Published
2005

38. A Clinical Study Provides the First Direct Evidence That Interindividual Variations in Fecal β-Lactamase Activity Affect the Gut Mycobiota Dynamics in Response to β-Lactam Antibiotics

Author

Delavy, Margot, primary, Burdet, Charles, additional, Sertour, Natacha, additional, Devente, Savannah, additional, Docquier, Jean-Denis, additional, Grall, Nathalie, additional, Volant, Stevenn, additional, Ghozlane, Amine, additional, Duval, Xavier, additional, Mentré, France, additional, d’Enfert, Christophe, additional, and Bougnoux, Marie-Elisabeth, additional

Published
2022
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45. S10.3c Clinical studies provide new insights on the association between the microbiota and host resistance to Candida albicans intestinal colonization

Author

Delavy, Margot, primary, Burdet, Charles, additional, Sertour, Natacha, additional, Chatelier, Emmanuelle Le, additional, Doquier, Jean-Denis, additional, Volant, Stevenn, additional, Ghozlane, Amine, additional, Grall, Nathalie, additional, Duval, Xavier, additional, Mentré, France, additional, Duffy, Darragh, additional, D'Enfert, Christophe, additional, and Bougnoux, Marie-Elisabeth, additional

Published
2022
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50. Candida albicans commensalism in the oral mucosa is favoured by limited virulence and metabolic adaptation

Author

Lemberg, Christina, de San Vicente, Kontxi Martinez, Fróis-Martins, Ricardo, Altmeier, Simon, Tran, Van Du T, Mertens, Sarah, Amorim-Vaz, Sara, Rai, Laxmi Shanker, d’Enfert, Christophe, Pagni, Marco, Sanglard, Dominique, LeibundGut-Landmann, Salomé, Universität Zürich [Zürich] = University of Zurich (UZH), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Institute of Microbiology [University of Lausanne] (IMUL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Swiss National Science Foundation to SLL (grants N˚ 310030_166206, CRSII5_173863, 310030_166206, CRSII5_173863 and CRSII3_141848), Fondation pour la Recherche Médicale (FRM, DBF20160635719), Swiss Federal Government, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 812969,H2020-MSCA-ITN-2018,FunHoMic(2019), University of Zurich, Krysan, Damian J, and LeibundGut-Landmann, Salomé

Subjects
2403 Immunology, Virulence, [SDV.BA]Life Sciences [q-bio]/Animal biology, 2404 Microbiology, Immunology, 2405 Parasitology, Mouth Mucosa, Microbiology, Fungal Proteins, Mice, 1311 Genetics, Candidiasis, Oral, Virology, Candida albicans, 1312 Molecular Biology, 2406 Virology, Genetics, 570 Life sciences, biology, Animals, Parasitology, Symbiosis, Molecular Biology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 10244 Institute of Virology
Abstract

International audience; As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces of the human body. Commensalism is tightly controlled by complex interactions of the fungus and the host to preclude fungal elimination but also fungal overgrowth and invasion, which can result in disease. As such, defects in antifungal T cell immunity render individuals susceptible to oral thrush due to interrupted immunosurveillance of the oral mucosa. The factors that promote commensalism and ensure persistence of C. albicans in a fully immunocompetent host remain less clear. Using an experimental model of C. albicans oral colonization in mice we explored fungal determinants of commensalism in the oral cavity. Transcript profiling of the oral isolate 101 in the murine tongue tissue revealed a characteristic metabolic profile tailored to the nutrient poor conditions in the stratum corneum of the epithelium where the fungus resides. Metabolic adaptation of isolate 101 was also reflected in enhanced nutrient acquisition when grown on oral mucosa substrates. Persistent colonization of the oral mucosa by C. albicans also correlated inversely with the capacity of the fungus to induce epithelial cell damage and to elicit an inflammatory response. Here we show that these immune evasive properties of isolate 101 are explained by a strong attenuation of a number of virulence genes, including those linked to filamentation. De-repression of the hyphal program by deletion or conditional repression of NRG1 abolished the commensal behaviour of isolate 101, thereby establishing a central role of this factor in the commensal lifestyle of C. albicans in the oral niche of the host.Author summary : The oral microbiota represents an important part of the human microbiota and includes several hundreds to several thousands of bacterial and fungal species. One of the most prominent fungus colonizing the oral cavity is the yeast Candida albicans. While the presence of C. albicans usually remains unnoticed, the fungus can under certain circumstances cause lesions on the lining of the mouth referred to as oral thrush or contribute to other common oral diseases such as caries. Maintaining C. albicans commensalism in the oral mucosa is therefore of utmost importance for oral health and overall wellbeing. While overt fungal growth and disease is limited by immunosurveillance mechanisms during homeostasis, C. albicans strives to survive and evades elimination from the host. Here, we show that while commensalism in the oral cavity is characterized by a restricted fungal virulence and hyphal program, enforcing filamentation in a commensal isolate is sufficient for driving pathogenicity and fungus-induced inflammation in the oral mucosa thwarting persistent colonization. Our results further support a critical role for specialized nutrient acquisition allowing the fungus to thrive in the nutrient poor environment of the squamous epithelium. Together, this work revealed key determinants of C. albicans commensalism in the oral niche.

Published
2022

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