Skip to main content
SpringerLink
Log in

Atmospheric humidity regulates same-sex mating in Candida albicans through the trehalose and osmotic signaling pathways

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

Sexual reproduction is prevalent in eukaryotic organisms and plays a critical role in the evolution of new traits and in the generation of genetic diversity. Environmental factors often have a direct impact on the occurrence and frequency of sexual reproduction in fungi. The regulatory effects of atmospheric relative humidity (RH) on sexual reproduction and pathogenesis in plant fungal pathogens and in soil fungi have been extensively investigated. However, the knowledge of how RH regulates the lifecycles of human fungal pathogens is limited. In this study, we report that low atmospheric RH promotes the development of mating projections and same-sex (homothallic) mating in the human fungal pathogen Candida albicans. Low RH causes water loss in C. albicans cells, which results in osmotic stress and the generation of intracellular reactive oxygen species (ROS) and trehalose. The water transporting aquaporin Aqy1, and the G-protein coupled receptor Gpr1 function as cell surface sensors of changes in atmospheric humidity. Perturbation of the trehalose metabolic pathway by inactivating trehalose synthase or trehalase promotes same-sex mating in C. albicans by increasing osmotic or ROS stresses, respectively. Intracellular trehalose and ROS signal the Hog1-osmotic and Hsf1-Hsp90 signaling pathways to regulate the mating response. We, therefore, propose that the cell surface sensors Aqy1 and Gpr1, intracellular trehalose and ROS, and the Hog1-osmotic and Hsf1-Hsp90 signaling pathways function coordinately to regulate sexual mating in response to low atmospheric RH conditions in C. albicans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Alby, K., and Bennett, R.J. (2009). Stress-induced phenotypic switching in Candida albicans. Mol Biol Cell 20, 3178–3191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alby, K., Schaefer, D., and Bennett, R.J. (2009). Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature 460, 890–893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson, J.M., and Soll, D.R. (1987). Unique phenotype of opaque cells in the white-opaque transition of Candida albicans. J Bacteriol 169, 5579–5588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Argüelles, J.C. (2000). Physiological roles of trehalose in bacteria and yeasts: a comparative analysis. Arch Microbiol 174, 217–224.

    Article  PubMed  Google Scholar 

  • Barton, N.H., and Charlesworth, B. (1998). Why sex and recombination? Science 281, 1986–1990.

    Article  CAS  PubMed  Google Scholar 

  • Bensasson, D., Dicks, J., Ludwig, J.M., Bond, C.J., Elliston, A., Roberts, I. N., and James, S.A. (2019). Diverse lineages of Candida albicans live on old oaks. Genetics 211, 277–288.

    Article  CAS  PubMed  Google Scholar 

  • Berman, J. (2012). Candida albicans. Curr Biol 22, R620–R622.

    Article  CAS  PubMed  Google Scholar 

  • Berman, J., and Hadany, L. (2012). Does stress induce (para)sex? Implications for Candida albicans evolution. Trends Genet 28, 197–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bulterys, PL., Le, T., Quang, V.M., Nelson, K.E., and Lloyd-Smith, J.O. (2013). Environmental predictors and incubation period of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Vietnam. Clin Infect Dis 56, 1273–1279.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheng, M.F., Yu, K.W., Tang, R.B., Fan, Y.H., Yang, Y.L., Hsieh, K.S., Ho, M., and Lo, H.J. (2004). Distribution and antifungal susceptibility of Candida species causing candidemia from 1996 to 1999. Diag Microbiol Infect Dis 48, 33–37.

    Article  CAS  Google Scholar 

  • Clarkson, J.P., Fawcett, L., Anthony, S.G., and Young, C. (2014). A model for Sclerotinia sclerotiorum infection and disease development in lettuce, based on the effects of temperature, relative humidity and ascospore density. PLoS ONE 9, e94049.

    Article  PubMed  PubMed Central  Google Scholar 

  • Coelho, M.A., Bakkeren, G., Sun, S., Hood, M.E., and Giraud, T. (2017). Fungal sex: the basidiomycota. Microbiol Spectr 5, FUNK–0046–2016.

    Article  CAS  Google Scholar 

  • Craik, V.B., Johnson, A.D., and Lohse, M.B. (2017). Sensitivity of white and opaque Candida albicans cells to antifungal drugs. Antimicrob Agents Chemother 61, e00166–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diezmann, S., Michaut, M., Shapiro, R.S., Bader, G.D., and Cowen, L.E. (2012). Mapping the Hsp90 genetic interaction network in Candida albicans reveals environmental contingency and rewired circuitry. PLoS Genet 8, e1002562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donders, G.G.G., Ruban, K., Donders, F., and Reybrouck, R. (2022). Lab-based retrospective 10-year analysis shows seasonal variation of vaginal Candida infection rates in Belgium. J Clin Med 11, 574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elbein, A.D., Pan, Y.T., Pastuszak, I., and Carroll, D. (2003). New insights on trehalose: a multifunctional molecule. Glycobiology 13, 17R–27.

    Article  CAS  PubMed  Google Scholar 

  • Eleutherio, E.C.A., de Araujo, P.S., and Panek, A.D. (1993). Role of the trehalose carrier in dehydration resistance of Saccharomyces cerevisiae. Biochim Biophys Acta 1156, 263–266.

    Article  CAS  PubMed  Google Scholar 

  • Enjalbert, B., Smith, D.A., Cornell, M.J., Alam, I., Nicholls, S., Brown, A. J.P., and Quinn, J. (2006). Role of the Hog1 stress-activated protein kinase in the global transcriptional response to stress in the fungal pathogen Candida albicans. Mol Biol Cell 17, 1018–1032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erkut, C., Gade, V.R., Laxman, S., and Kurzchalia, T.V. (2016). The glyoxylate shunt is essential for desiccation tolerance in C. elegans and budding yeast. eLife 5, e13614.

    Article  PubMed  PubMed Central  Google Scholar 

  • Estruch, F. (2000). Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast. FEMS Microbiol Rev 24, 469–486.

    Article  CAS  PubMed  Google Scholar 

  • Feofilova, E.P., Usov, A.I., Mysyakina, I.S., and Kochkina, G.A. (2014). Trehalose: chemical structure, biological functions, and practical application. Microbiology 83, 184–194.

    Article  CAS  Google Scholar 

  • Forche, A., Abbey, D., Pisithkul, T., Weinzierl, M.A., Ringstrom, T., Bruck, D., Petersen, K., and Berman, J. (2011). Stress alters rates and types of loss of heterozygosity in Candida albicans. mBio 2, e00129–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Granke, L.L., and Hausbeck, M.K. (2010). Effects of temperature, humidity, and wounding on development of phytophthora rot of cucumber fruit. Plant Dis 94, 1417–1424.

    Article  CAS  PubMed  Google Scholar 

  • Guan, G., Tao, L., Yue, H., Liang, W., Gong, J., Bing, J., Zheng, Q., Veri, A.O., Fan, S., Robbins, N., et al. (2019). Environment-induced samesex mating in the yeast Candida albicans through the Hsf1-Hsp90 pathway. PLoS Biol 17, e2006966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guinea, J. (2014). Global trends in the distribution of Candida species causing candidemia. Clin Microbiol Infect 20, 5–10.

    Article  PubMed  Google Scholar 

  • Hassine, M., Siah, A., Hellin, P., Cadalen, T., Halama, P., Hilbert, J.L., Hamada, W., Baraket, M., Yahyaoui, A., Legrève, A., et al. (2019). Sexual reproduction of Zymoseptoria tritici on durum wheat in Tunisia revealed by presence of airborne inoculum, fruiting bodies and high levels of genetic diversity. Fungal Biol 123, 763–772.

    Article  CAS  PubMed  Google Scholar 

  • Hirakawa, M.P., Chyou, D.E., Huang, D., Slan, A.R., and Bennett, R.J. (2017). Parasex generates phenotypic diversity de novo and impacts drug resistance and virulence in Candida albicans. Genetics 207, 1195–1211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, G., Srikantha, T., Sahni, N., Yi, S., and Soll, D.R. (2009). CO2 regulates white-to-opaque switching in Candida albicans. Curr Biol 19, 330–334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, G., Wang, H., Chou, S., Nie, X., Chen, J., and Liu, H. (2006). Bistable expression of WOR1, a master regulator of white–opaque switching in Candida albicans. Proc Natl Acad Sci USA 103, 12813–12818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain, N.K., and Roy, I. (2009). Effect of trehalose on protein structure. Protein Sci 18, 24–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Khoo, P., Cabrera-Aguas, M.P., Nguyen, V., Lahra, M.M., and Watson, S.L. (2020). Microbial keratitis in Sydney, Australia: risk factors, patient outcomes, and seasonal variation. Graefes Arch Clin Exp Ophthalmol 258, 1745–1755.

    Article  PubMed  Google Scholar 

  • Kis-Papo, T., Kirzhner, V., Wasser, S.P., and Nevo, E. (2003). Evolution of genomic diversity and sex at extreme environments: fungal life under hypersaline Dead Sea stress. Proc Natl Acad Sci USA 100, 14970–14975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, Y., Uddin, W., and Kaminski, J.E. (2014). Effects of relative humidity on infection, colonization and conidiation of Magnaporthe orzyae on perennial ryegrass. Plant Pathol 63, 590–597.

    Article  CAS  Google Scholar 

  • Lillie, S.H., and Pringle, J.R. (1980). Reserve carbohydrate metabolism in Saccharomyces cerevisiae: responses to nutrient limitation. J Bacteriol 143, 1384–1394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manstretta, V., and Rossi, V. (2016). Effects of temperature and moisture on development of Fusarium graminearum perithecia in maize stalk residues. Appl Environ Microbiol 82, 184–191.

    Article  CAS  PubMed  Google Scholar 

  • Miller, M.G., and Johnson, A.D. (2002). White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110, 293–302.

    Article  CAS  PubMed  Google Scholar 

  • Mok, W.Y., Luizão, R.C., do Socorro Barreto da Silva, M., Teixeira, M.F., and Muniz, E.G. (1984). Ecology of pathogenic yeasts in Amazonian soil. Appl Environ Microbiol 47, 390–394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ni, M., Feretzaki, M., Sun, S., Wang, X., and Heitman, J. (2011). Sex in fungi. Annu Rev Genet 45, 405–430.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noble, S.M., and Johnson, A.D. (2005). Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot Cell 4, 298–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nunn, M.A., Schäfer, S.M., Petrou, M.A., and Brown, J.R.M. (2007). Environmental source of Candida dubliniensis. Emerg Infect Dis 13, 747–750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Brien, C.E., Oliveira-Pacheco, J., Cinnéide, E.O., Haase, M.A.B., Hittinger, C.T., Rogers, T.R., Zaragoza, O., Bond, U., and Butler, G. (2021). Population genomics of the pathogenic yeast Candida tropicalis identifies hybrid isolates in environmental samples. PLoS Pathog 17, e1009138.

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Meara, T.R., Veri, A.O., Polvi, E.J., Li, X., Valaei, S.F., Diezmann, S., and Cowen, L.E. (2016). Mapping the Hsp90 genetic network reveals ergosterol biosynthesis and phosphatidylinositol-4-kinase signaling as core circuitry governing cellular stress. PLoS Genet 11, e1006142.

    Article  Google Scholar 

  • Opulente, D.A., Langdon, Q.K., Buh, K.V., Haase, M.A.B., Sylvester, K., Moriarty, R.V., Jarzyna, M., Considine, S.L., Schneider, R.M., and Hittinger, C.T. (2019). Pathogenic budding yeasts isolated outside of clinical settings. FEMS Yeast Res 19, foz031.

    Article  Google Scholar 

  • Paul, P.A., and Munkvold, G.P. (2005). Influence of temperature and relative humidity on sporulation of Cercospora zeae-maydis and expansion of gray leaf spot lesions on maize leaves. Plant Dis 89, 624–630.

    Article  CAS  PubMed  Google Scholar 

  • Pfaller, M.A., Diekema, D.J., and International Fungal Surveillance Participant, G. (2004). Twelve years of fluconazole in clinical practice: global trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida. Clin Microbiol Infect 10, 11–23.

    Article  CAS  PubMed  Google Scholar 

  • Reuß, O., Vik, Å., Kolter, R., and Morschhäuser, J. (2004). The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341, 119–127.

    Article  PubMed  Google Scholar 

  • Rodaki, A., Bohovych, I.M., Enjalbert, B., Young, T., Odds, F.C., Gow, N. A., and Brown, A.J. (2009). Glucose promotes stress resistance in the fungal pathogen Candida albicans. Mol Biol Cell 20, 4845–4855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulze, U., Larsen, M.E., and Villadsen, J. (1995). Determination of intracellular trehalose and glycogen in Saccharomyces cerevisiae. Anal Biochem 228, 143–149.

    Article  CAS  PubMed  Google Scholar 

  • Serneels, J., Tournu, H., and Van Dijck, P. (2012). Tight control of trehalose content is required for efficient heat-induced cell elongation in Candida albicans. J Biol Chem 287, 36873–36882.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma, B., and Nonzom, S. (2021). Superficial mycoses, a matter of concern: Global and Indian scenario—an updated analysis. Mycoses 64, 890–908.

    Article  PubMed  Google Scholar 

  • Singer, M.A., and Lindquist, S. (1998). Multiple effects of trehalose on protein folding in vitro and in vivo. Mol Cell 1, 639–648.

    Article  CAS  PubMed  Google Scholar 

  • Slutsky, B., Staebell, M., Anderson, J., Risen, L., Pfaller, M., and Soll, D.R. (1981). “White-opaque transition”: a second high-frequency switching system in Candida albicans. J Bacteriol 169, 189–191.

    Article  Google Scholar 

  • Soveral, G., Prista, C., Moura, T.F., and Loureiro-Dias, M.C. (2011). Yeast water channels: an overview of orthodox aquaporins. Biol Cell 103, 35–54.

    Article  CAS  Google Scholar 

  • Sun, Y., Gadoury, C., Hirakawa, M.P., Bennett, R.J., Harcus, D., Marcil, A., and Whiteway, M. (2016). Deletion of a Yci1 domain protein of Candida albicans allows homothallic mating in MTL heterozygous cells. mBio 7, e00465–00416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tao, L., Cao, C., Liang, W., Guan, G., Zhang, Q., Nobile, C.J., and Huang, G. (2014). White cells facilitate opposite- and same-sex mating of opaque cells in Candida albicans. PLoS Genet 10, e1004737.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tapia, H., Young, L., Fox, D., Bertozzi, C.R., and Koshland, D. (2015). Increasing intracellular trehalose is sufficient to confer desiccation tolerance to Saccharomyces cerevisiae. Proc Natl Acad Sci USA 112, 6122–6127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Velásquez, A.C., Castroverde, C.D.M., and He, S.Y. (2018). Plant-pathogen warfare under changing climate conditions. Curr Biol 28, R619–R634.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wallen, R.M., and Perlin, M.H. (2018). An overview of the function and maintenance of sexual reproduction in dikaryotic fungi. Front Microbiol 9, 503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallen, R.M., Richardson, K., Furnish, M., Mendoza, H., Dentinger, A., Khanal, S., and Perlin, M.H. (2021). Hungry for sex: differential roles for Ustilago maydisb locus components in haploid cells vis à vis nutritional availability. J Fungi 7, 135.

    Article  CAS  Google Scholar 

  • Wiemken, A. (1990). Trehalose in yeast, stress protectant rather than reserve carbohydrate. Antonie van Leeuwenhoek 58, 209–217.

    Article  CAS  PubMed  Google Scholar 

  • Xiao, M., Chen, S.C.A., Kong, F., Xu, X.L., Yan, L., Kong, H.S., Fan, X., Hou, X., Cheng, J.W., Zhou, M.L., et al. (2020). Distribution and antifungal susceptibility of Candida species causing candidemia in China: an update from the CHIF-NET study. J Infect Dis 221, S139–S147.

    Article  PubMed  Google Scholar 

  • Zaragoza, O., Blazquez, M.A., and Gancedo, C. (1998). Disruption of the Candida albicans TPS1 gene encoding trehalose-6-phosphate synthase impairs formation of hyphae and decreases infectivity. J Bacteriol 180, 3809–3815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2021YFC2300400), the National Natural Science Foundation of China (31930005 and 32170194), and Shanghai Municipal Science and Technology Major Project (HS2021SHZX001). This work was also supported by the National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) award R35GM124594, and by the Kamangar family in the form of an endowed chair to C.J.N. The content is the sole responsibility of the authors and does not represent the views of the funders. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. We thank all members of the Huang and Nobile labs for feedback on the manuscript.

Author information

Author notes

  1. Contributed equally to this work

Authors and Affiliations

  1. Department of Infectious Diseases, Huashan Hospital, Shanghai Institute of Infectious Disease and Biosecurity and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China

    Chao Li, Li Tao, Guobo Guan, Zhangyue Guan, Tianren Hu, Jian Bing, Ming Xu & Guanghua Huang

  2. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China

    Chao Li & Guobo Guan

  3. Department of Molecular and Cell Biology, University of California, Merced, Merced, CA, 95343, USA

    Austin M. Perry & Clarissa J. Nobile

  4. Quantitative and Systems Biology Graduate Program, University of California, Merced, Merced, CA, 95343, USA

    Austin M. Perry

  5. Health Sciences Research Institute, University of California, Merced, Merced, CA, 95343, USA

    Clarissa J. Nobile

  6. Shanghai Engineering Research Center of Industrial Microorganisms, Shanghai, 200438, China

    Guanghua Huang

  7. Shanghai Huashen Institute of Microbes and Infections, Shanghai, 200052, China

    Guanghua Huang

Authors
  1. Chao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guobo Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhangyue Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Austin M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tianren Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jian Bing
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ming Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Clarissa J. Nobile
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guanghua Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guanghua Huang.

Ethics declarations

Compliance and ethics Clarissa J. Nobile is a cofounder of BioSynesis, Inc., a company developing diagnostics and therapeutics for biofilm infections. The other authors declare that they have no conflict of interest.

Supporting information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, C., Tao, L., Guan, G. et al. Atmospheric humidity regulates same-sex mating in Candida albicans through the trehalose and osmotic signaling pathways. Sci. China Life Sci. 66, 1915–1929 (2023). https://doi.org/10.1007/s11427-023-2309-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-023-2309-1

Keywords

Search

Navigation