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Transcription factors Asg1p and Hal9p regulate pH homeostasis in Candida glabrata.

ABSTRACT: Candida glabrata is an important microorganism used in commercial fermentation to produce pyruvate, but very little is known about its mechanisms for surviving acid stress in culture. In this study, it was shown that transcription factors Asg1p and Hal9p play essential roles in C. glabrata in the tolerance of acid stress, as the deletion of CgASG1 or CgHAL9 resulted in the inability to survive in an acidic environment. Cgasg1? and Cghal9? mutant strains are unable to maintain pH homeostasis, as evidenced by a decrease in intracellular pH and an increase in reactive oxygen species production, which results in metabolic disorders. The results showed that intracellular acidification was partly due to the diminished activity of the plasma membrane proton pump, CgPma1p. In addition, transcriptome sequencing revealed that Cgasg1? and Cghal9? mutant strains displayed a variety of changes in gene expression under acidic conditions, including genes in the MAPK signaling pathway, plasma membrane, or cell wall organization, trehalose accumulation, and the RIM101 signaling pathway. Lastly, quantitative reverse-transcribed PCR and cellular localization showed that CgAsg1p and CgHal9p played independent roles in response to acid stress.

SUBMITTER: Wu J

PROVIDER: S-EPMC4539521 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Transcription factors Asg1p and Hal9p regulate pH homeostasis in Candida glabrata.

Wu Jing J Chen Xiulai X Cai Lijun L Tang Lei L Liu Liming L

Frontiers in microbiology 20150818

Candida glabrata is an important microorganism used in commercial fermentation to produce pyruvate, but very little is known about its mechanisms for surviving acid stress in culture. In this study, it was shown that transcription factors Asg1p and Hal9p play essential roles in C. glabrata in the tolerance of acid stress, as the deletion of CgASG1 or CgHAL9 resulted in the inability to survive in an acidic environment. Cgasg1Δ and Cghal9Δ mutant strains are unable to maintain pH homeostasis, as ...[more]

PMID: 26347728

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Project description:The human fungal pathogen Candida albicans colonizes and infects various host sites with diverse environmental pH. Adaptation to these diverse pH conditions plays a crucial role in its success as a commensal and pathogen. The conserved Rim101 pH sensing pathway is responsible for neutral-alkaline pH responses in C. albicans. In this study, we identified a novel Rfg1-Bcr1 regulatory pathway that governs acidic pH responses and regulates filamentation in C. albicans. A null mutant library was screened, and we have identified Rfg1 and Bcr1 as key regulators of filamentation under acidic pH conditions. Rfg1 directly binds to the promoter region of Bcr1 to regulate its transcriptional expression, which in turn suppresses the filamentation of C. albicans. PHR1, an alkaline pH response gene, is significantly activated by the absence of Rfg1, indicating that Rfg1 regulates acidic pH response through the Rim101-Phr1 pathway. Moreover, the cAMP signaling pathway, transcription factors Efg1 and Flo8, and the hyphal-specific G1 cyclin Hgc1 play critical roles in the regulation. Our findings provide new insights into the mechanisms underlying the acidic pH response of C. albicans, which reflects its elaborate regulatory control of environmental adaptation.IMPORTANCECandida albicans is a human commensal and frequent pathogen that encounters a wide range of pH stresses. The ability of C. albicans to adapt to changes in extracellular pH is crucial for its success in colonization and pathogenesis. The Rim101 pH sensing pathway is well known to govern neutral-alkaline pH responses in this pathogen. Here, we report a novel Rfg1-Bcr1 regulatory pathway that governs acidic pH responses and regulates filamentous growth in C. albicans. In addition, the Rim101-Phr1 pathway, cAMP signaling pathway, transcription factors Efg1 and Flo8, and hyphal-specific G1 cyclin Hgc1 cooperate with this regulation. Our findings provide new insights into the regulatory mechanism of acidic pH response in C. albicans.

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Transcription factors Asg1p and Hal9p regulate pH homeostasis in Candida glabrata.

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Transcription factors Asg1p and Hal9p regulate pH homeostasis in Candida glabrata.

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