ER Stress Response Mechanisms in the Pathogenic Yeast Candida Glabrata and Their Roles in Virulence

Overview

Journal Virulence

Specialty Microbiology

Date 2013 Dec 17

PMID 24335436

Citations 15

Authors

Taiga Miyazaki

Shigeru Kohno

Affiliations

Soon will be listed here.

Abstract

The maintenance of endoplasmic reticulum (ER) homeostasis is critical for numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation of misfolded proteins in the ER (ER stress) by activating the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the folding capacity of the ER. Recent studies of several pathogenic fungi have revealed that the UPR is important for antifungal resistance and virulence; therefore, the pathway has attracted much attention as a potential therapeutic target. While the UPR is highly conserved among eukaryotes, our group recently discovered that the pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses alternative mechanisms to cope with ER stress. This review summarizes how C. glabrata responds to ER stress and discusses the impacts of ER quality control systems on antifungal resistance and virulence.

Citing Articles

Phosphate availability conditions caspofungin tolerance, capsule attachment and titan cell formation in .

Qu X, Bhalla K, Horianopoulos L, Hu G, Magana A, Foster L Front Fungal Biol. 2024; 5:1447588.

PMID: 39206133 PMC: 11349702. DOI: 10.3389/ffunb.2024.1447588.

Unmasking of CgYor1-Dependent Azole Resistance Mediated by Target of Rapamycin (TOR) and Calcineurin Signaling in Candida glabrata.

Kumari S, Kumar M, Esquivel B, Wasi M, Pandey A, Khandelwal N mBio. 2022; 13(1):e0354521.

PMID: 35038899 PMC: 8764518. DOI: 10.1128/mbio.03545-21.

Protomer alignment modulates specificity of RNA substrate recognition by Ire1.

Li W, Crotty K, Ruiz D, Voorhies M, Rivera C, Sil A Elife. 2021; 10.

PMID: 33904404 PMC: 8104961. DOI: 10.7554/eLife.67425.

The involvement of the trehalase enzymes in stress resistance and gut colonization.

Van Ende M, Timmermans B, Vanreppelen G, Siscar-Lewin S, Fischer D, Wijnants S Virulence. 2020; 12(1):329-345.

PMID: 33356857 PMC: 7808424. DOI: 10.1080/21505594.2020.1868825.

The Unfolded Protein Response Regulates Pathogenic Development of Ustilago maydis by Rok1-Dependent Inhibition of Mating-Type Signaling.

Schmitz L, Schwier M, Heimel K mBio. 2019; 10(6).

PMID: 31848283 PMC: 6918084. DOI: 10.1128/mBio.02756-19.

References

Pfaller M, Neofytos D, Diekema D, Azie N, Meier-Kriesche H, Quan S . Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance®) registry, 2004-2008. Diagn Microbiol Infect Dis. 2012; 74(4):323-31. DOI: 10.1016/j.diagmicrobio.2012.10.003. View

Hollien J, Lin J, Li H, Stevens N, Walter P, Weissman J . Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol. 2009; 186(3):323-31. PMC: 2728407. DOI: 10.1083/jcb.200903014. View

Mori K, Kawahara T, Yoshida H, Yanagi H, Yura T . Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway. Genes Cells. 1996; 1(9):803-17. DOI: 10.1046/j.1365-2443.1996.d01-274.x. View

Pfaller M, Diekema D . Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007; 20(1):133-63. PMC: 1797637. DOI: 10.1128/CMR.00029-06. View

Klionsky D . Autophagy. Curr Biol. 2005; 15(8):R282-3. DOI: 10.1016/j.cub.2005.04.013. View

Feng X, Krishnan K, Richie D, Aimanianda V, Hartl L, Grahl N . HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus. PLoS Pathog. 2011; 7(10):e1002330. PMC: 3197630. DOI: 10.1371/journal.ppat.1002330. View

Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S, Lafontaine I . Genome evolution in yeasts. Nature. 2004; 430(6995):35-44. DOI: 10.1038/nature02579. View

Rutkowski D, Hegde R . Regulation of basal cellular physiology by the homeostatic unfolded protein response. J Cell Biol. 2010; 189(5):783-94. PMC: 2878945. DOI: 10.1083/jcb.201003138. View

Dudgeon D, Zhang N, Ositelu O, Kim H, Cunningham K . Nonapoptotic death of Saccharomyces cerevisiae cells that is stimulated by Hsp90 and inhibited by calcineurin and Cmk2 in response to endoplasmic reticulum stresses. Eukaryot Cell. 2008; 7(12):2037-51. PMC: 2593186. DOI: 10.1128/EC.00291-08. View

10.

Walter P, Ron D . The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011; 334(6059):1081-6. DOI: 10.1126/science.1209038. View

11.

Pfaller M . Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med. 2011; 125(1 Suppl):S3-13. DOI: 10.1016/j.amjmed.2011.11.001. View

12.

Weissman Z, Shemer R, Conibear E, Kornitzer D . An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans. Mol Microbiol. 2008; 69(1):201-17. DOI: 10.1111/j.1365-2958.2008.06277.x. View

13.

Travers K, Patil C, Wodicka L, Lockhart D, Weissman J, Walter P . Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell. 2000; 101(3):249-58. DOI: 10.1016/s0092-8674(00)80835-1. View

14.

Han D, Lerner A, Vande Walle L, Upton J, Xu W, Hagen A . IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell. 2009; 138(3):562-75. PMC: 2762408. DOI: 10.1016/j.cell.2009.07.017. View

15.

Hollien J, Weissman J . Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science. 2006; 313(5783):104-7. DOI: 10.1126/science.1129631. View

16.

Miyazaki T, Inamine T, Yamauchi S, Nagayoshi Y, Saijo T, Izumikawa K . Role of the Slt2 mitogen-activated protein kinase pathway in cell wall integrity and virulence in Candida glabrata. FEMS Yeast Res. 2010; 10(3):343-52. DOI: 10.1111/j.1567-1364.2010.00611.x. View

17.

Richie D, Feng X, Hartl L, Aimanianda V, Krishnan K, Powers-Fletcher M . The virulence of the opportunistic fungal pathogen Aspergillus fumigatus requires cooperation between the endoplasmic reticulum-associated degradation pathway (ERAD) and the unfolded protein response (UPR). Virulence. 2011; 2(1):12-21. PMC: 3073235. DOI: 10.4161/viru.2.1.13345. View

18.

Cox J, Shamu C, Walter P . Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell. 1993; 73(6):1197-206. DOI: 10.1016/0092-8674(93)90648-a. View

19.

Torres-Quiroz F, Garcia-Marques S, Coria R, Randez-Gil F, Prieto J . The activity of yeast Hog1 MAPK is required during endoplasmic reticulum stress induced by tunicamycin exposure. J Biol Chem. 2010; 285(26):20088-96. PMC: 2888421. DOI: 10.1074/jbc.M109.063578. View

20.

Bonilla M, Cunningham K . Mitogen-activated protein kinase stimulation of Ca(2+) signaling is required for survival of endoplasmic reticulum stress in yeast. Mol Biol Cell. 2003; 14(10):4296-305. PMC: 207020. DOI: 10.1091/mbc.e03-02-0113. View