Competitive fungal commensalism mitigates candidiasis pathology

Jarmila Sekeresova Kralova; Catalina Donic; Bareket Dassa; Ilana Livyatan; Paul Mathias Jansen; Shifra Ben-Dor; Lena Fidel; Sébastien Trzebanski; Lian Narunsky-Haziza; Omer Asraf; Ori Brenner; Hagit Dafni; Ghil Jona; Sigalit Boura-Halfon; Noa Stettner; Eran Segal; Sascha Brunke; Yitzhak Pilpel; Ravid Straussman; David Zeevi; Petra Bacher; Bernhard Hube; Neta Shlezinger; Steffen Jung

doi:10.1084/jem.20231686

Competitive fungal commensalism mitigates candidiasis pathology

Jarmila Sekeresova Kralova, Catalina Donic, Bareket Dassa, Ilana Livyatan, Paul Mathias Jansen, Shifra Ben-Dor, Lena Fidel, Sébastien Trzebanski, Lian Narunsky-Haziza, Omer Asraf, Ori Brenner, Hagit Dafni, Ghil Jona, Sigalit Boura-Halfon, Noa Stettner, Eran Segal, Sascha Brunke, Yitzhak Pilpel, Ravid Straussman, David ZeeviPetra Bacher, Bernhard Hube, Neta Shlezinger, Steffen Jung^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

The mycobiota are a critical part of the gut microbiome, but host–fungal interactions and specific functional contributions of commensal fungi to host fitness remain incompletely understood. Here, we report the identification of a new fungal commensal, Kazachstania heterogenica var. weizmannii, isolated from murine intestines. K. weizmannii exposure prevented Candida albicans colonization and significantly reduced the commensal C. albicans burden in colonized animals. Following immunosuppression of C. albicans colonized mice, competitive fungal commensalism thereby mitigated fatal candidiasis. Metagenome analysis revealed K. heterogenica or K. weizmannii presence among human commensals. Our results reveal competitive fungal commensalism within the intestinal microbiota, independent of bacteria and immune responses, that could bear potential therapeutic value for the management of C. albicans–mediated diseases.

Original language	English
Article number	e20231686
Journal	Journal of Experimental Medicine
Volume	221
Issue number	5
Early online date	18 Mar 2024
DOIs	https://doi.org/10.1084/jem.20231686
Publication status	Published - 6 May 2024

Bibliographical note

We would like to thank J. Berman (Tel Aviv University, Tel Aviv, Israel) for providing the recombinant C. albicans (SC5314) reporter strain, Travis W. Adkins, (NRRL collection) for prompt yeast delivery, J. Zahradnik and G. Schreiber (Weizmann Institute, Rehovot, Israel) for the plasmid encoding the modified miRFP670 fluorescent protein, M. Lotan-Pompan and A. Weinberger for help with the bioinformatic analysis, S. Schäuble and M. Mirhakkak for providing the R script for the Biolog data analysis, C. Bar-Natan for help with the germ-free animal experiment, and L.P. Coelho for helping with access to the metagenomes.

S. Jung was funded by the Israeli Science Foundation (grant #696/21) and by the Bridge, Innovate, Nurture, Advance program of the Weizmann Institute. This research was generously supported by Morris Kahn Institute for Human Immunology. S. Jung is the incumbent of the Henry H. Drake Professorial Chair of Immunology. P.M. Jansen, S. Brunke, and B. Hube were funded by the Deutsche Forschungsgemeinschaft (DFG) through the Cluster of Excellence “Balance of the Microverse,” DFG project number 390713860. P. Bacher was funded by the Cluster of Excellence EXC2167 “Precision Medicine in Chronic Inflammation,” Project ID 390884018.

Author contributions: J. Sekeresova Kralova made the initial observation and conceived the project with S. Jung. C. Donic performed the yeast quantifications and serum titer analysis. S. Boura-Halfon and S. Trzebanski provided animals and helped with analysis. S. Ben-Dor and L. Fidel performed the genome analysis. B. Dassa, I. Livyatan, L. Narunsky-Haziza, O. Asraf, D. Zeevi, E. Segal, Y. Pilpel, and R. Straussman contributed the human microbiome analysis. P. Bacher performed human T cell analysis. P.M. Jansen, S. Brunke, and B. Hube performed the Biolog analysis. G. Jona helped with yeast culture. O. Brenner performed histology. H. Dafni and N. Stettner helped with the sentinel screen and germ-free analysis. N. Stettner advised on yeast biology and helped in generating the reporter strain. P. Bacher, B. Hube, S. Brunke, J.S. Kralova, and S. Jung wrote the manuscript.

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

Access to Document

10.1084/jem.20231686Licence: CC BY-NC-SA

Cite this

Sekeresova Kralova, J., Donic, C., Dassa, B., Livyatan, I., Jansen, P. M., Ben-Dor, S., Fidel, L., Trzebanski, S., Narunsky-Haziza, L., Asraf, O., Brenner, O., Dafni, H., Jona, G., Boura-Halfon, S., Stettner, N., Segal, E., Brunke, S., Pilpel, Y., Straussman, R., ... Jung, S. (2024). Competitive fungal commensalism mitigates candidiasis pathology. Journal of Experimental Medicine, 221(5), Article e20231686. https://doi.org/10.1084/jem.20231686

@article{0e0ea42ffe6d4053bdca7449364223ad,

title = "Competitive fungal commensalism mitigates candidiasis pathology",

abstract = "The mycobiota are a critical part of the gut microbiome, but host–fungal interactions and specific functional contributions of commensal fungi to host fitness remain incompletely understood. Here, we report the identification of a new fungal commensal, Kazachstania heterogenica var. weizmannii, isolated from murine intestines. K. weizmannii exposure prevented Candida albicans colonization and significantly reduced the commensal C. albicans burden in colonized animals. Following immunosuppression of C. albicans colonized mice, competitive fungal commensalism thereby mitigated fatal candidiasis. Metagenome analysis revealed K. heterogenica or K. weizmannii presence among human commensals. Our results reveal competitive fungal commensalism within the intestinal microbiota, independent of bacteria and immune responses, that could bear potential therapeutic value for the management of C. albicans–mediated diseases.",

author = "{Sekeresova Kralova}, Jarmila and Catalina Donic and Bareket Dassa and Ilana Livyatan and Jansen, {Paul Mathias} and Shifra Ben-Dor and Lena Fidel and S{\'e}bastien Trzebanski and Lian Narunsky-Haziza and Omer Asraf and Ori Brenner and Hagit Dafni and Ghil Jona and Sigalit Boura-Halfon and Noa Stettner and Eran Segal and Sascha Brunke and Yitzhak Pilpel and Ravid Straussman and David Zeevi and Petra Bacher and Bernhard Hube and Neta Shlezinger and Steffen Jung",

note = "We would like to thank J. Berman (Tel Aviv University, Tel Aviv, Israel) for providing the recombinant C. albicans (SC5314) reporter strain, Travis W. Adkins, (NRRL collection) for prompt yeast delivery, J. Zahradnik and G. Schreiber (Weizmann Institute, Rehovot, Israel) for the plasmid encoding the modified miRFP670 fluorescent protein, M. Lotan-Pompan and A. Weinberger for help with the bioinformatic analysis, S. Sch{\"a}uble and M. Mirhakkak for providing the R script for the Biolog data analysis, C. Bar-Natan for help with the germ-free animal experiment, and L.P. Coelho for helping with access to the metagenomes. S. Jung was funded by the Israeli Science Foundation (grant #696/21) and by the Bridge, Innovate, Nurture, Advance program of the Weizmann Institute. This research was generously supported by Morris Kahn Institute for Human Immunology. S. Jung is the incumbent of the Henry H. Drake Professorial Chair of Immunology. P.M. Jansen, S. Brunke, and B. Hube were funded by the Deutsche Forschungsgemeinschaft (DFG) through the Cluster of Excellence “Balance of the Microverse,” DFG project number 390713860. P. Bacher was funded by the Cluster of Excellence EXC2167 “Precision Medicine in Chronic Inflammation,” Project ID 390884018. Author contributions: J. Sekeresova Kralova made the initial observation and conceived the project with S. Jung. C. Donic performed the yeast quantifications and serum titer analysis. S. Boura-Halfon and S. Trzebanski provided animals and helped with analysis. S. Ben-Dor and L. Fidel performed the genome analysis. B. Dassa, I. Livyatan, L. Narunsky-Haziza, O. Asraf, D. Zeevi, E. Segal, Y. Pilpel, and R. Straussman contributed the human microbiome analysis. P. Bacher performed human T cell analysis. P.M. Jansen, S. Brunke, and B. Hube performed the Biolog analysis. G. Jona helped with yeast culture. O. Brenner performed histology. H. Dafni and N. Stettner helped with the sentinel screen and germ-free analysis. N. Stettner advised on yeast biology and helped in generating the reporter strain. P. Bacher, B. Hube, S. Brunke, J.S. Kralova, and S. Jung wrote the manuscript.",

year = "2024",

month = may,

day = "6",

doi = "10.1084/jem.20231686",

language = "English",

volume = "221",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "5",

}

Sekeresova Kralova, J, Donic, C , Dassa, B, Livyatan, I, Jansen, PM, Ben-Dor, S, Fidel, L, Trzebanski, S, Narunsky-Haziza, L, Asraf, O, Brenner, O , Dafni, H , Jona, G , Boura-Halfon, S, Stettner, N, Segal, E, Brunke, S, Pilpel, Y , Straussman, R , Zeevi, D, Bacher, P, Hube, B, Shlezinger, N & Jung, S 2024, 'Competitive fungal commensalism mitigates candidiasis pathology', Journal of Experimental Medicine, vol. 221, no. 5, e20231686. https://doi.org/10.1084/jem.20231686

TY - JOUR

T1 - Competitive fungal commensalism mitigates candidiasis pathology

AU - Sekeresova Kralova, Jarmila

AU - Donic, Catalina

AU - Dassa, Bareket

AU - Livyatan, Ilana

AU - Jansen, Paul Mathias

AU - Ben-Dor, Shifra

AU - Fidel, Lena

AU - Trzebanski, Sébastien

AU - Narunsky-Haziza, Lian

AU - Asraf, Omer

AU - Brenner, Ori

AU - Dafni, Hagit

AU - Jona, Ghil

AU - Boura-Halfon, Sigalit

AU - Stettner, Noa

AU - Segal, Eran

AU - Brunke, Sascha

AU - Pilpel, Yitzhak

AU - Straussman, Ravid

AU - Zeevi, David

AU - Bacher, Petra

AU - Hube, Bernhard

AU - Shlezinger, Neta

AU - Jung, Steffen

N1 - We would like to thank J. Berman (Tel Aviv University, Tel Aviv, Israel) for providing the recombinant C. albicans (SC5314) reporter strain, Travis W. Adkins, (NRRL collection) for prompt yeast delivery, J. Zahradnik and G. Schreiber (Weizmann Institute, Rehovot, Israel) for the plasmid encoding the modified miRFP670 fluorescent protein, M. Lotan-Pompan and A. Weinberger for help with the bioinformatic analysis, S. Schäuble and M. Mirhakkak for providing the R script for the Biolog data analysis, C. Bar-Natan for help with the germ-free animal experiment, and L.P. Coelho for helping with access to the metagenomes. S. Jung was funded by the Israeli Science Foundation (grant #696/21) and by the Bridge, Innovate, Nurture, Advance program of the Weizmann Institute. This research was generously supported by Morris Kahn Institute for Human Immunology. S. Jung is the incumbent of the Henry H. Drake Professorial Chair of Immunology. P.M. Jansen, S. Brunke, and B. Hube were funded by the Deutsche Forschungsgemeinschaft (DFG) through the Cluster of Excellence “Balance of the Microverse,” DFG project number 390713860. P. Bacher was funded by the Cluster of Excellence EXC2167 “Precision Medicine in Chronic Inflammation,” Project ID 390884018. Author contributions: J. Sekeresova Kralova made the initial observation and conceived the project with S. Jung. C. Donic performed the yeast quantifications and serum titer analysis. S. Boura-Halfon and S. Trzebanski provided animals and helped with analysis. S. Ben-Dor and L. Fidel performed the genome analysis. B. Dassa, I. Livyatan, L. Narunsky-Haziza, O. Asraf, D. Zeevi, E. Segal, Y. Pilpel, and R. Straussman contributed the human microbiome analysis. P. Bacher performed human T cell analysis. P.M. Jansen, S. Brunke, and B. Hube performed the Biolog analysis. G. Jona helped with yeast culture. O. Brenner performed histology. H. Dafni and N. Stettner helped with the sentinel screen and germ-free analysis. N. Stettner advised on yeast biology and helped in generating the reporter strain. P. Bacher, B. Hube, S. Brunke, J.S. Kralova, and S. Jung wrote the manuscript.

PY - 2024/5/6

Y1 - 2024/5/6

N2 - The mycobiota are a critical part of the gut microbiome, but host–fungal interactions and specific functional contributions of commensal fungi to host fitness remain incompletely understood. Here, we report the identification of a new fungal commensal, Kazachstania heterogenica var. weizmannii, isolated from murine intestines. K. weizmannii exposure prevented Candida albicans colonization and significantly reduced the commensal C. albicans burden in colonized animals. Following immunosuppression of C. albicans colonized mice, competitive fungal commensalism thereby mitigated fatal candidiasis. Metagenome analysis revealed K. heterogenica or K. weizmannii presence among human commensals. Our results reveal competitive fungal commensalism within the intestinal microbiota, independent of bacteria and immune responses, that could bear potential therapeutic value for the management of C. albicans–mediated diseases.

AB - The mycobiota are a critical part of the gut microbiome, but host–fungal interactions and specific functional contributions of commensal fungi to host fitness remain incompletely understood. Here, we report the identification of a new fungal commensal, Kazachstania heterogenica var. weizmannii, isolated from murine intestines. K. weizmannii exposure prevented Candida albicans colonization and significantly reduced the commensal C. albicans burden in colonized animals. Following immunosuppression of C. albicans colonized mice, competitive fungal commensalism thereby mitigated fatal candidiasis. Metagenome analysis revealed K. heterogenica or K. weizmannii presence among human commensals. Our results reveal competitive fungal commensalism within the intestinal microbiota, independent of bacteria and immune responses, that could bear potential therapeutic value for the management of C. albicans–mediated diseases.

UR - http://www.scopus.com/inward/record.url?scp=85188045493&partnerID=8YFLogxK

U2 - 10.1084/jem.20231686

DO - 10.1084/jem.20231686

M3 - Article

SN - 0022-1007

VL - 221

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 5

M1 - e20231686

ER -

Competitive fungal commensalism mitigates candidiasis pathology

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this