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

Lookup NU author(s): Alessandra da Silva Dantas, Dr Miranda Morton, Professor Brian Morgan, Professor Janet Quinn

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Abstract

The ability of the major systemic fungal pathogen of humans, Candida albicans, to sense and respond to reactive oxygen species (ROS), such as H(2)O(2) 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 H(2)O(2)-induced phosphorylation of the Hog1 stress-activated protein kinase and to reverse H(2)O(2)-induced oxidation and activation of the AP-1 like transcription factor Cap1. Furthermore, Trx1 regulates H(2)O(2)-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 H(2)O(2) signaling and promotes C. albicans survival in the host.


Publication metadata

Author(s): da Silva Dantas A, Patterson MJ, Smith DA, MacCallum DM, Erwig LP, Morgan BA, Quinn J

Publication type: Article

Journal: Molecular and Cellular Biology

Year: 2010

Volume: 30

Issue: 19

Pages: 4550-4563

Print publication date: 02/08/2010

ISSN (print): 0270-7306

ISSN (electronic): 1098-5549

Publisher: American Society of Microbiology

URL: http://dx.doi.org/10.1128/MCB.00313-10

DOI: 10.1128/MCB.00313-10


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