Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris

Alison M. Day; Megan M. McNiff; Alessandra da Silva Dantas; Neil A.R. Gow; Janet Quinn

doi:10.1128/mSphere.00506-18

Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris

Alison M. Day^*, Megan M. McNiff, Alessandra da Silva Dantas, Neil A.R. Gow, Janet Quinn

^*Corresponding author for this work

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

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Abstract

Candida auris has recently emerged as an important, multidrug-resistant fungal pathogen of humans. Comparative studies indicate that despite high levels of genetic divergence, C. auris is as virulent as the most pathogenic member of the genus, Candida albicans. However, key virulence attributes of C. albicans, such as morphogenetic switching, are not utilized by C. auris, indicating that this emerging pathogen employs alternative strategies to infect and colonize the host. An important trait required for the pathogenicity of many fungal pathogens is the ability to adapt to host-imposed stresses encountered during infection. Here, we investigated the relative resistance of C. auris and other pathogenic Candida species to physiologically relevant stresses and explored the role of the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK) in promoting stress resistance and virulence. In comparison to C. albicans, C. auris is relatively resistant to hydrogen peroxide, cationic stress, and cell-wall-damaging agents. However, in contrast to other Candida species examined, C. auris was unable to grow in an anaerobic environment and was acutely sensitive to organic oxidative-stress-inducing agents. An analysis of C. auris hog1? cells revealed multiple roles for this SAPK in stress resistance, cell morphology, aggregation, and virulence. These data demonstrate that C. auris has a unique stress resistance profile compared to those of other pathogenic Candida species and that the Hog1 SAPK has pleiotropic roles that promote the virulence of this emerging pathogen.

Original language	English
Article number	e00506-18
Journal	mSphere
Volume	3
Issue number	5
DOIs	https://doi.org/10.1128/mSphere.00506-18
Publication status	Published - 24 Oct 2018

Bibliographical note

We thank Elizabeth Johnson and Adrien Szekely from the Mycology Reference Laboratory, Public Health England, for the clinical C. auris isolates used in this study. We also thank Katharina Trunk for comments on the manuscript.

This work was funded by the BBSRC (BB/K016393/1, BB/P020119/1) and the Wellcome Trust (097377/101873).

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Keywords

Candida auris
Pathogenesis
Stress adaptation
Stress kinases

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10.1128/mSphere.00506-18Licence: CC BY

Hog1 Regulates Stress Tolerance and Virulence in the Emerging Fungal Pathogen Candida auris
Copyright © 2018 Day et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0/
Final published version, 2.98 MBLicence: CC BY

Cite this

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title = "Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris",

abstract = "Candida auris has recently emerged as an important, multidrug-resistant fungal pathogen of humans. Comparative studies indicate that despite high levels of genetic divergence, C. auris is as virulent as the most pathogenic member of the genus, Candida albicans. However, key virulence attributes of C. albicans, such as morphogenetic switching, are not utilized by C. auris, indicating that this emerging pathogen employs alternative strategies to infect and colonize the host. An important trait required for the pathogenicity of many fungal pathogens is the ability to adapt to host-imposed stresses encountered during infection. Here, we investigated the relative resistance of C. auris and other pathogenic Candida species to physiologically relevant stresses and explored the role of the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK) in promoting stress resistance and virulence. In comparison to C. albicans, C. auris is relatively resistant to hydrogen peroxide, cationic stress, and cell-wall-damaging agents. However, in contrast to other Candida species examined, C. auris was unable to grow in an anaerobic environment and was acutely sensitive to organic oxidative-stress-inducing agents. An analysis of C. auris hog1? cells revealed multiple roles for this SAPK in stress resistance, cell morphology, aggregation, and virulence. These data demonstrate that C. auris has a unique stress resistance profile compared to those of other pathogenic Candida species and that the Hog1 SAPK has pleiotropic roles that promote the virulence of this emerging pathogen.",

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note = "We thank Elizabeth Johnson and Adrien Szekely from the Mycology Reference Laboratory, Public Health England, for the clinical C. auris isolates used in this study. We also thank Katharina Trunk for comments on the manuscript. This work was funded by the BBSRC (BB/K016393/1, BB/P020119/1) and the Wellcome Trust (097377/101873). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.",

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N1 - We thank Elizabeth Johnson and Adrien Szekely from the Mycology Reference Laboratory, Public Health England, for the clinical C. auris isolates used in this study. We also thank Katharina Trunk for comments on the manuscript. This work was funded by the BBSRC (BB/K016393/1, BB/P020119/1) and the Wellcome Trust (097377/101873). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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N2 - Candida auris has recently emerged as an important, multidrug-resistant fungal pathogen of humans. Comparative studies indicate that despite high levels of genetic divergence, C. auris is as virulent as the most pathogenic member of the genus, Candida albicans. However, key virulence attributes of C. albicans, such as morphogenetic switching, are not utilized by C. auris, indicating that this emerging pathogen employs alternative strategies to infect and colonize the host. An important trait required for the pathogenicity of many fungal pathogens is the ability to adapt to host-imposed stresses encountered during infection. Here, we investigated the relative resistance of C. auris and other pathogenic Candida species to physiologically relevant stresses and explored the role of the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK) in promoting stress resistance and virulence. In comparison to C. albicans, C. auris is relatively resistant to hydrogen peroxide, cationic stress, and cell-wall-damaging agents. However, in contrast to other Candida species examined, C. auris was unable to grow in an anaerobic environment and was acutely sensitive to organic oxidative-stress-inducing agents. An analysis of C. auris hog1? cells revealed multiple roles for this SAPK in stress resistance, cell morphology, aggregation, and virulence. These data demonstrate that C. auris has a unique stress resistance profile compared to those of other pathogenic Candida species and that the Hog1 SAPK has pleiotropic roles that promote the virulence of this emerging pathogen.

AB - Candida auris has recently emerged as an important, multidrug-resistant fungal pathogen of humans. Comparative studies indicate that despite high levels of genetic divergence, C. auris is as virulent as the most pathogenic member of the genus, Candida albicans. However, key virulence attributes of C. albicans, such as morphogenetic switching, are not utilized by C. auris, indicating that this emerging pathogen employs alternative strategies to infect and colonize the host. An important trait required for the pathogenicity of many fungal pathogens is the ability to adapt to host-imposed stresses encountered during infection. Here, we investigated the relative resistance of C. auris and other pathogenic Candida species to physiologically relevant stresses and explored the role of the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK) in promoting stress resistance and virulence. In comparison to C. albicans, C. auris is relatively resistant to hydrogen peroxide, cationic stress, and cell-wall-damaging agents. However, in contrast to other Candida species examined, C. auris was unable to grow in an anaerobic environment and was acutely sensitive to organic oxidative-stress-inducing agents. An analysis of C. auris hog1? cells revealed multiple roles for this SAPK in stress resistance, cell morphology, aggregation, and virulence. These data demonstrate that C. auris has a unique stress resistance profile compared to those of other pathogenic Candida species and that the Hog1 SAPK has pleiotropic roles that promote the virulence of this emerging pathogen.

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Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris

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