Dataset Information

The Potassium Transporter Hak1 in Candida Albicans, Regulation and Physiological Effects at Limiting Potassium and under Acidic Conditions.

ABSTRACT: The three families of yeast plasma membrane potassium influx transporters are represented in Candida albicans: Trk, Acu, and Hak proteins. Hak transporters work as K+-H+ symporters, and the genes coding for Hak proteins are transcriptionally activated under potassium limitation. This work shows that C. albicans mutant cells lacking CaHAK1 display a severe growth impairment at limiting potassium concentrations under acidic conditions. This is the consequence of a defective capacity to transport K+, as indicated by potassium absorption experiments and by the kinetics parameters of Rb+ (K+) transport. Moreover, hak1- cells are more sensitive to the toxic cation lithium. All these phenotypes became much less robust or even disappeared at alkaline growth conditions. Finally, transcriptional studies demonstrate that the hak1- mutant, in comparison with HAK1+ cells, activates the expression of the K+/Na+ ATPase coded by CaACU1 in the presence of Na+ or in the absence of K+.

SUBMITTER: Ruiz-Castilla FJ

PROVIDER: S-EPMC8148600 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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The Potassium Transporter Hak1 in Candida Albicans, Regulation and Physiological Effects at Limiting Potassium and under Acidic Conditions.

Ruiz-Castilla Francisco J FJ Rodríguez-Castro Elisa E Michán Carmen C Ramos José J

Journal of fungi (Basel, Switzerland) 20210506 5

The three families of yeast plasma membrane potassium influx transporters are represented in Candida albicans: Trk, Acu, and Hak proteins. Hak transporters work as K+-H+ symporters, and the genes coding for Hak proteins are transcriptionally activated under potassium limitation. This work shows that C. albicans mutant cells lacking CaHAK1 display a severe growth impairment at limiting potassium concentrations under acidic conditions. This is the consequ ...[more]

PMID: 34066565

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Project description:The vaginal acidic environment potentiates the formation of Candida glabrata biofilms, leading to complicated and recurrent infections. Importantly, the production of matrix is known to contribute to the recalcitrant features of Candida biofilms. In this study, we reveal that Zap1 regulates the matrix of C. glabrata acidic biofilms and analyzed the modulation of their transcriptome (by microarrays) and matrix proteome (by LC-MS/MS) by Zap1. For that, the deletion mutant zap1Δ and its complemented strain zap1Δ::ZAP1 were constructed, and their biofilms were developed at pH 4 (adjusted with lactic acid). The results revealed that Zap1 is a negative regulator of the total amount of protein and carbohydrate in the biofilm matrix. Accordingly, various genes and matrix proteins with predicted functions in the regulation of carbohydrate metabolism, sugar binding, sugar transport, and adhesion (including Epa family) were repressed by Zap1. Nevertheless, the results also suggested that Zap1 is essential to the delivery and organization of some matrix components. Indeed, Zap1 was required for the secretion of 122 proteins to the matrix and induced the expression of 557 genes, including various targets involved in glucan metabolism. Additionally, Zap1 induced targets with roles in virulence, resistance to antifungals, and host immunity evasion, including yapsins, ERG family, and moonlighting proteins. Zap1 was also required for the secretion of acidic-specific matrix proteins, indicating a contribution to the response to the acidic environment. Overall, this study demonstrates that Zap1 is a relevant regulator of the biofilm matrix, contributing to a better understanding of C. glabrata acidic biofilms.IMPORTANCEThe rising prevalence of vulvovaginal candidiasis (VVC) and the increasing presence of Candida spp. with aggressive virulence features and low susceptibility to common antifungals, particularly Candida glabrata, have resulted in more severe, prolonged, and recurrent cases of VVC, with significant implications for patients. This research offers valuable insights into the molecular changes that contribute to the formation of C. glabrata biofilms in the acidic vaginal environment, representing a significant advancement in the understanding of C. glabrata's virulence. Notably, this study identified Zap1 as a critical regulator of C. glabrata biofilm matrix, with additional potential roles in adhesion, antifungal resistance, evasion of host immunity, and response to acidic conditions, making it a promising target for new therapeutic approaches. Importantly, Zap1 is the first regulator of the biofilm matrix to be identified in C. glabrata, and the elucidation of its targets (including genes and matrix proteins) lays a strong foundation for future research.

Dataset Information

The Potassium Transporter Hak1 in Candida Albicans, Regulation and Physiological Effects at Limiting Potassium and under Acidic Conditions.

Publications

The Potassium Transporter Hak1 in <i>Candida Albicans,</i> Regulation and Physiological Effects at Limiting Potassium and under Acidic Conditions.

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