Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in Candida albicans

Alessandra da Silva Dantas, Miranda J Patterson, Deborah A Smith, Donna M MacCallum, Lars P Erwig, Brian A Morgan, Janet Quinn

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The ability of the major systemic fungal pathogen of humans, Candida albicans, to sense and respond to reactive oxygen species (ROS), such as H2O2 generated by the host immune system, is required for survival in the host. However, the intracellular signaling mechanisms underlying such responses are poorly understood. Here, we show that thioredoxin (Trx1), in addition to its antioxidant activity, plays a central role in coordinating the response of C. albicans to ROS by regulating multiple pathways. In particular, Trx1 function is important for H2O2-induced phosphorylation of the Hog1 stress-activated protein kinase and to reverse H2O2-induced oxidation and activation of the AP-1 like transcription factor Cap1. Furthermore, Trx1 regulates H2O2-induced hyperpolarized bud growth in a mechanism that involves activation of the Rad53 checkpoint kinase. Consistent with its key roles in responses to ROS, cells lacking Trx1 displayed significantly attenuated virulence in a murine model of C. albicans systemic infection. Collectively, our data indicate that Trx1 has a multifaceted role in H2O2 signaling and promotes C. albicans survival in the host.
Original languageEnglish
Pages (from-to) 4550-4563
Number of pages14
JournalMolecular and Cellular Biology
Volume30
Issue number19
Early online date2 Aug 2010
DOIs
Publication statusPublished - Oct 2010

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Thioredoxins
Candida albicans
Hydrogen Peroxide
Reactive Oxygen Species
Transcription Factor AP-1
Heat-Shock Proteins
Protein Kinases
Virulence
Immune System
Phosphotransferases
Antioxidants
Phosphorylation
Survival
Growth
Infection

Cite this

da Silva Dantas, A., Patterson, M. J., Smith, D. A., MacCallum, D. M., Erwig, L. P., Morgan, B. A., & Quinn, J. (2010). Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in Candida albicans. Molecular and Cellular Biology, 30(19), 4550-4563 . https://doi.org/10.1128/MCB.00313-10

Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in Candida albicans. / da Silva Dantas, Alessandra; Patterson, Miranda J; Smith, Deborah A; MacCallum, Donna M; Erwig, Lars P; Morgan, Brian A; Quinn, Janet.

In: Molecular and Cellular Biology, Vol. 30, No. 19, 10.2010, p. 4550-4563 .

Research output: Contribution to journalArticle

da Silva Dantas, A, Patterson, MJ, Smith, DA, MacCallum, DM, Erwig, LP, Morgan, BA & Quinn, J 2010, 'Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in Candida albicans', Molecular and Cellular Biology, vol. 30, no. 19, pp. 4550-4563 . https://doi.org/10.1128/MCB.00313-10
da Silva Dantas, Alessandra ; Patterson, Miranda J ; Smith, Deborah A ; MacCallum, Donna M ; Erwig, Lars P ; Morgan, Brian A ; Quinn, Janet. / Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in Candida albicans. In: Molecular and Cellular Biology. 2010 ; Vol. 30, No. 19. pp. 4550-4563 .
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