The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives

Christophe d'Enfert; Ann-Kristin Kaune; Leovigildo Rey Alaban; Sayoni  Chakraborty; Nathaniel Cole; Margot  Delavy; Daria Kosmala; Benoît  Marsaux; Ricardo  FróisMartins; Moran  Morelli; Diletta  Rosati; Marisa  Valentine; Zixuan  Xie; Yoan  Emritloll; Peter A  Warn; Frédéric Bequet; Marie-Elisabeth Bougnoux; Stephanie  Bornes; Mark S.  Gresnigt; Bernard Hube; lse D.  Jacobsen; Melanie Legrand; Salomé Leibundgut-Landmann; Chaysavanh Manichanh; Carol Munro; Mihai G. Netea; Karla  Queiroz; Karine  Roget; Vincent  Thomas; Claudia  Thora; Pieter Van den Abbeele; Alan W Walker; Alistair J.P.  Brown

doi:10.1093/femsre/fuaa060

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives

Christophe d'Enfert^* (Corresponding Author), Ann-Kristin Kaune, Leovigildo Rey Alaban, Sayoni Chakraborty, Nathaniel Cole, Margot Delavy, Daria Kosmala, Benoît Marsaux, Ricardo FróisMartins, Moran Morelli, Diletta Rosati, Marisa Valentine, Zixuan Xie, Yoan Emritloll, Peter A Warn, Frédéric Bequet, Marie-Elisabeth Bougnoux, Stephanie Bornes, Mark S. Gresnigt , Bernard Hubelse D. Jacobsen, Melanie Legrand, Salomé Leibundgut-Landmann, Chaysavanh Manichanh, Carol Munro, Mihai G. Netea, Karla Queiroz, Karine Roget, Vincent Thomas, Claudia Thora, Pieter Van den Abbeele, Alan W Walker, Alistair J.P. Brown^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

144 Citations (Scopus)

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Abstract

Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

Original language	English
Article number	fuaa060
Number of pages	55
Journal	FEMS Microbiology Reviews
Volume	45
Issue number	3
Early online date	24 Nov 2020
DOIs	https://doi.org/10.1093/femsre/fuaa060
Publication status	Published - May 2021

Bibliographical note

ACKNOWLEDGEMENTS:
We thank our friends and colleagues in the medical mycology, fungal immunology and microbiota fields for many thought-provoking discussions.
FUNDING:
We received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action, Innovative Training Network: FunHoMic; grant N° 812969. CdE received funding from the French Government ‘Investissement d’Avenir’ program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004), the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507). SLL and CdE received funding from the Swiss National Science Foundation (Sinergia program, #CRSII5_173863). BIOASTER received funding from the French Government ‘Investissement d’Avenir’ program (Grant No. ANR-10-AIRT-03). MSG was supported by a Humboldt Research Fellowship for Postdoctoral Researchers by the Alexander von Humboldt-Foundation and the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Program (project no. 434385622 / GR 5617/1-1). BH was supported by the Deutsche Forschungsgemeinschaft (DFG) project Hu 532/20-1, project C1 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal
infections” - HDM-FUN (Grant Agreement 847507), the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (215599/Z/19/Z). IDJ was supported by the Deutsche orschungsgemeinschaft (DFG) project C5 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (Grant 215599/Z/19/Z). CM received funding from the the Instituto de Salud
Carlos III/FEDER. MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. CAM was supported by EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” -HDM-FUN (Grant Agreement 847507) and the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). AWW receives core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services
(RESAS). AJPB was supported by a programme grant from the UK Medical Research Council (MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology at the University of Exeter (MR/N006364/1).

Keywords

Candida
candida infections
antifungal immunity
microbiota
mycobiota
fungus-host-microbiota interactions
patients variability
fungal variability
microbiota variability

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Cite this

d'Enfert, C., Kaune, A.-K., Rey Alaban, L., Chakraborty, S., Cole, N., Delavy, M., Kosmala, D., Marsaux, B., FróisMartins, R., Morelli, M., Rosati, D., Valentine, M., Xie, Z., Emritloll, Y., Warn, P. A., Bequet, F., Bougnoux, M.-E., Bornes, S., Gresnigt , M. S., ... Brown, A. J. P. (2021). The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiology Reviews, 45(3), Article fuaa060. https://doi.org/10.1093/femsre/fuaa060

d'Enfert, C, Kaune, A-K, Rey Alaban, L, Chakraborty, S, Cole, N, Delavy, M, Kosmala, D, Marsaux, B, FróisMartins, R, Morelli, M, Rosati, D, Valentine, M, Xie, Z, Emritloll, Y, Warn, PA, Bequet, F, Bougnoux, M-E, Bornes, S, Gresnigt , MS, Hube, B, Jacobsen, LD, Legrand, M, Leibundgut-Landmann, S, Manichanh, C, Munro, C, Netea, MG, Queiroz, K, Roget, K, Thomas, V, Thora, C, Van den Abbeele, P, Walker, AW & Brown, AJP 2021, 'The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives', FEMS Microbiology Reviews, vol. 45, no. 3, fuaa060. https://doi.org/10.1093/femsre/fuaa060

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title = "The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives",

abstract = "Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.",

keywords = "Candida, candida infections, antifungal immunity, microbiota, mycobiota, fungus-host-microbiota interactions, patients variability, fungal variability, microbiota variability",

author = "Christophe d'Enfert and Ann-Kristin Kaune and {Rey Alaban}, Leovigildo and Sayoni Chakraborty and Nathaniel Cole and Margot Delavy and Daria Kosmala and Beno{\^i}t Marsaux and Ricardo Fr{\'o}isMartins and Moran Morelli and Diletta Rosati and Marisa Valentine and Zixuan Xie and Yoan Emritloll and Warn, {Peter A} and Fr{\'e}d{\'e}ric Bequet and Marie-Elisabeth Bougnoux and Stephanie Bornes and Gresnigt, {Mark S.} and Bernard Hube and Jacobsen, {lse D.} and Melanie Legrand and Salom{\'e} Leibundgut-Landmann and Chaysavanh Manichanh and Carol Munro and Netea, {Mihai G.} and Karla Queiroz and Karine Roget and Vincent Thomas and Claudia Thora and {Van den Abbeele}, Pieter and Walker, {Alan W} and Brown, {Alistair J.P.}",

note = "ACKNOWLEDGEMENTS: We thank our friends and colleagues in the medical mycology, fungal immunology and microbiota fields for many thought-provoking discussions. FUNDING: We received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action, Innovative Training Network: FunHoMic; grant N° 812969. CdE received funding from the French Government {\textquoteleft}Investissement d{\textquoteright}Avenir{\textquoteright} program (Laboratoire d{\textquoteright}Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004), the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507). SLL and CdE received funding from the Swiss National Science Foundation (Sinergia program, #CRSII5_173863). BIOASTER received funding from the French Government {\textquoteleft}Investissement d{\textquoteright}Avenir{\textquoteright} program (Grant No. ANR-10-AIRT-03). MSG was supported by a Humboldt Research Fellowship for Postdoctoral Researchers by the Alexander von Humboldt-Foundation and the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Program (project no. 434385622 / GR 5617/1-1). BH was supported by the Deutsche Forschungsgemeinschaft (DFG) project Hu 532/20-1, project C1 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507), the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (215599/Z/19/Z). IDJ was supported by the Deutsche orschungsgemeinschaft (DFG) project C5 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (Grant 215599/Z/19/Z). CM received funding from the the Instituto de Salud Carlos III/FEDER. MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. CAM was supported by EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” -HDM-FUN (Grant Agreement 847507) and the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). AWW receives core funding support from the Scottish Government{\textquoteright}s Rural and Environment Science and Analytical Services (RESAS). AJPB was supported by a programme grant from the UK Medical Research Council (MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology at the University of Exeter (MR/N006364/1).",

year = "2021",

month = may,

doi = "10.1093/femsre/fuaa060",

language = "English",

volume = "45",

journal = "FEMS Microbiology Reviews",

issn = "0168-6445",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections

T2 - current knowledge and new perspectives

AU - d'Enfert, Christophe

AU - Kaune, Ann-Kristin

AU - Rey Alaban, Leovigildo

AU - Chakraborty, Sayoni

AU - Cole, Nathaniel

AU - Delavy, Margot

AU - Kosmala, Daria

AU - Marsaux, Benoît

AU - FróisMartins, Ricardo

AU - Morelli, Moran

AU - Rosati, Diletta

AU - Valentine, Marisa

AU - Xie, Zixuan

AU - Emritloll, Yoan

AU - Warn, Peter A

AU - Bequet, Frédéric

AU - Bougnoux, Marie-Elisabeth

AU - Bornes, Stephanie

AU - Gresnigt , Mark S.

AU - Hube, Bernard

AU - Jacobsen, lse D.

AU - Legrand, Melanie

AU - Leibundgut-Landmann, Salomé

AU - Manichanh, Chaysavanh

AU - Munro, Carol

AU - Netea, Mihai G.

AU - Queiroz, Karla

AU - Roget, Karine

AU - Thomas, Vincent

AU - Thora, Claudia

AU - Van den Abbeele, Pieter

AU - Walker, Alan W

AU - Brown, Alistair J.P.

N1 - ACKNOWLEDGEMENTS: We thank our friends and colleagues in the medical mycology, fungal immunology and microbiota fields for many thought-provoking discussions. FUNDING: We received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action, Innovative Training Network: FunHoMic; grant N° 812969. CdE received funding from the French Government ‘Investissement d’Avenir’ program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004), the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507). SLL and CdE received funding from the Swiss National Science Foundation (Sinergia program, #CRSII5_173863). BIOASTER received funding from the French Government ‘Investissement d’Avenir’ program (Grant No. ANR-10-AIRT-03). MSG was supported by a Humboldt Research Fellowship for Postdoctoral Researchers by the Alexander von Humboldt-Foundation and the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Program (project no. 434385622 / GR 5617/1-1). BH was supported by the Deutsche Forschungsgemeinschaft (DFG) project Hu 532/20-1, project C1 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507), the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (215599/Z/19/Z). IDJ was supported by the Deutsche orschungsgemeinschaft (DFG) project C5 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (Grant 215599/Z/19/Z). CM received funding from the the Instituto de Salud Carlos III/FEDER. MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. CAM was supported by EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” -HDM-FUN (Grant Agreement 847507) and the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). AWW receives core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS). AJPB was supported by a programme grant from the UK Medical Research Council (MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology at the University of Exeter (MR/N006364/1).

PY - 2021/5

Y1 - 2021/5

N2 - Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

AB - Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

KW - Candida

KW - candida infections

KW - antifungal immunity

KW - microbiota

KW - mycobiota

KW - fungus-host-microbiota interactions

KW - patients variability

KW - fungal variability

KW - microbiota variability

U2 - 10.1093/femsre/fuaa060

DO - 10.1093/femsre/fuaa060

M3 - Review article

C2 - 33232448

SN - 0168-6445

VL - 45

JO - FEMS Microbiology Reviews

JF - FEMS Microbiology Reviews

IS - 3

M1 - fuaa060

ER -

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives

Abstract

Bibliographical note

Keywords

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