Candida albicans HSP12 is co-regulated by physiological CO2 and pH

Sheth, Chirag C.; Mogensen, Estelle; Fu, Man Shun; Blomfield, Ian C.; Mühlschlegel, Fritz A.

doi:10.1016/j.fgb.2008.04.004

Cited by 16 publications

(14 citation statements)

References 26 publications

(30 reference statements)

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“…Interestingly, among the 14 genes whose expressions are significantly changed by high CO 2 , three of them (HSP12, AAH1, and OPT1) are known to be regulated by the HOG pathway (Sheth et al 2008), indicating that CO 2 sensing and metabolism could also be related to the stress-response signaling pathway in C. albicans. Particularly, transcript abundance of HSP12, which encodes a small heat-shock protein involved in protein folding under stress conditions, are lowered by 5.5% CO 2 in an adenylyl cyclase/cAMP-dependent manner, suggesting that C. albicans considers ambient air having 0.036% CO 2 as stress.…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Analysis of the CO2 Sensing Pathway Via Differential Expression of Carbonic Anhydrase in Cryptococcus neoformans

Kim

Maeng

et al. 2010

Genetics

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Carbon dioxide (CO2) sensing and metabolism via carbonic anhydrases (CAs) play pivotal roles in survival and proliferation of pathogenic fungi infecting human hosts from natural environments due to the drastic difference in CO2 levels. In Cryptococcus neoformans, which causes fatal fungal meningoencephalitis, the Can2 CA plays essential roles during both cellular growth in air and sexual differentiation of the pathogen. However the signaling networks downstream of Can2 are largely unknown. To address this question, the present study employed comparative transcriptome DNA microarray analysis of a C. neoformans strain in which CAN2 expression is artificially controlled by the CTR4 (copper transporter) promoter. The PCTR4∷CAN2 strain showed growth defects in a CO2-dependent manner when CAN2 was repressed but resumed normal growth when CAN2 was overexpressed. The Can2-dependent genes identified by the transcriptome analysis include FAS1 (fatty acid synthase 1) and GPB1 (G-protein β subunit), supporting the roles of Can2 in fatty acid biosynthesis and sexual differentiation. Cas3, a capsular structure designer protein, was also discovered to be Can2-dependent and yet was not involved in CO2-mediated capsule induction. Most notably, a majority of Can2-dependent genes were environmental stress-regulated (ESR) genes. Supporting this, the CAN2 overexpression strain was hypersensitive to oxidative and genotoxic stress as well as antifungal drugs, such as polyene and azole drugs, potentially due to defective membrane integrity. Finally, an oxidative stress-responsive Atf1 transcription factor was also found to be Can2-dependent. Atf1 not only plays an important role in diverse stress responses, including thermotolerance and antifungal drug resistance, but also represses melanin and capsule production in C. neoformans. In conclusion, this study provides insights into the comprehensive signaling networks orchestrated by CA/CO2-sensing pathways in pathogenic fungi.

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Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Analysis of the CO2 Sensing Pathway Via Differential Expression of Carbonic Anhydrase in Cryptococcus neoformans

Kim

Maeng

et al. 2010

Genetics

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“…This reflects the relatively conservative nature of the false discovery methodology commonly used for determining significance in transcriptional differences and shows the utility of whole genome epistatic studies in improving the efficiency of gene discovery in microarray experiments. Hsp12 has been recently found to display cAMP-dependent gene transcription in fungal pathogens Candida albicans and C. neoformans and was found in the latter to have a role in polyene antifungal drug susceptibility (43,44). Interestingly, the majority of the population of Cn SP1/PKC1-dependent genes (151 of 163) were also induced in the WT strain during transition from mid-log phase growth FIGURE 6.…”

Section: Table 1 Constituent Expression Of Cn Sp1 Partially Restores mentioning

confidence: 99%

A Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in Cryptococcus neoformans

Adler

Park

Larsen

et al. 2011

Journal of Biological Chemistry

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Eukaryotic cells utilize complex signaling systems to detect their environments, responding and adapting as new conditions arise during evolution. The basidiomycete fungus Cryptococcus neoformans is a leading cause of AIDS-related death worldwide and utilizes the calcineurin and protein kinase C-1 (Pkc1) signaling pathways for host adaptation and expression of virulence. In the present studies, a C-terminal zinc finger transcription factor, homologous both to the calcineurin-responsive zinc fingers (Crz1) of ascomycetes and to the Pkc1-dependent specificity protein-1 (Sp1) transcription factors of metazoans, was identified and named SP1 because of its greater similarity to the metazoan factors. Structurally, the Cryptococcus neoformans Sp1 (Cn Sp1) protein was found to have acquired an additional zinc finger motif from that of Crz1 and showed Pkc1-dependent phosphorylation, nuclear localization, and whole genome epistatic associations under starvation conditions. Transcriptional targets of Cn Sp1 shared functional similarities with Crz1 factors, such as cell wall synthesis, but gained the regulation of processes involved in carbohydrate metabolism, including trehalose metabolism, and lost others, such as the induction of autophagy. In addition, overexpression of Cn Sp1 in a pkc1⌬ mutant showed restoration of altered phenotypes involved in virulence, including cell wall stability, nitrosative stress, and extracellular capsule production. Cn Sp1 was also found to be important for virulence of the fungus using a mouse model. In summary, these data suggest an evolutionary shift in C-terminal zinc finger proteins during fungal evolution, transforming them from calcineurin-dependent to PKC1-dependent transcription factors, helping to shape the role of fungal pathogenesis of C. neoformans.

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“…Hsp12, a small heat shock protein conserved among fungal species (41,42), is induced during stationary-phase growth and under stress conditions, including heat shock, osmotic, and oxidative stress in C. albicans (42). In the wild-type cells, HSP12 was greatly induced in response to both heat shock stress (25°C to 35°C) and cold shock stress (25°C to 4°C) (Fig.…”

Section: Candida Albicansmentioning

confidence: 99%

Distinct and Redundant Roles of the Two MYST Histone Acetyltransferases Esa1 and Sas2 in Cell Growth and Morphogenesis of Candida albicans

et al. 2013

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Candida albicans is associated with humans, as both a harmless commensal organism and a pathogen. Adaption to human body temperature is extremely important for its growth and morphogenesis. Saccharomyces cerevisiae Esa1, a member of the MYST family HATs (histone acetyltransferases) and the catalytic subunit of the NuA4 complex, and its homologues in other eukaryotes have been shown to be essential for cell growth. To investigate the functional roles of two MYST family HATs, Esa1 and Sas2 in C. albicans, we deleted ESA1 and SAS2 in the C. albicans genome and performed cell growth analyses. Our results demonstrated that C. albicans Esa1 is not essential for general growth but is essential for filamentous growth. The esa1/esa1 mutant cells exhibited sensitivity to thermal, genotoxic, and oxidative stresses but tolerance to cold, osmotic, and cell wall stresses. In contrast, the sas2/sas2 mutant adapted to growth at higher temperatures and promoted filament formation at lower temperatures, resembling the phenotype of a C. albicans strain overexpressing ESA1. Cells with deletions of both ESA1 and SAS2 were inviable, reflecting the functional redundancy in cell growth. C. albicans Esa1 and Sas2 have distinct and synergistic effects on histone acetylation at H4K5, H4K12, and H4K16. Esa1 contributes mainly to acetylation of H4K5 and H4K12, whereas Sas2 contributes to acetylation of H4K16. Our findings suggest that C. albicans Esa1 and Sas2 play opposite roles in cell growth and morphogenesis and contribute coordinately to histone acetylation and gene regulation.

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Candida albicans HSP12 is co-regulated by physiological CO2 and pH

Cited by 16 publications

References 26 publications

Comparative Transcriptome Analysis of the CO2 Sensing Pathway Via Differential Expression of Carbonic Anhydrase in Cryptococcus neoformans

Comparative Transcriptome Analysis of the CO2 Sensing Pathway Via Differential Expression of Carbonic Anhydrase in Cryptococcus neoformans

A Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in Cryptococcus neoformans

Distinct and Redundant Roles of the Two MYST Histone Acetyltransferases Esa1 and Sas2 in Cell Growth and Morphogenesis of Candida albicans

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