Iron Acquisition in the Pathobiology of Candida albicans

Srivastav, Manjit Kumar; Nair, Remya; Natarajan, Krishnamurthy

doi:10.1007/978-3-319-50409-4_17

Cited by 3 publications

(4 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, C. albicans and other fungal pathogens maintain iron homeostasis by modulating their intracellular iron pool through multiple iron acquisition pathways and by conserving iron pools by downregulating iron-requiring proteins. The iron homeostasis gene regulation is controlled by multiple transcriptional regulators in C. albicans and other fungi ( 4 , 6 , 9 ). Previous work had shown that transcriptional regulators Sef1, HAP complex, Hap43, and Sfu1 control iron homeostasis gene regulation by promoter binding ( 10 , 11 , 13 , 14 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…Iron is an essential micronutrient required for various metabolic steps, but has poor bioavailability in the mammalian host with vastly different concentrations in blood stream, gastrointestinal tract, and deep-seated tissues ( 3 ). Thus C. albicans has evolved multiple iron uptake strategies to mobilize iron from extracellular sources (reviewed in ( 4 , 5 , 6 , 7 , 8 , 9 )).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interplay between transcriptional regulators and the SAGA chromatin modifying complex fine-tune iron homeostasis

Srivastav¹,

Agarwal²,

Poonia

et al. 2021

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Interplay between transcriptional regulators and the SAGA chromatin modifying complex fine-tune iron homeostasis

Srivastav¹,

Agarwal²,

Poonia

et al. 2021

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Iron homeostasis gene expression in C. albicans is controlled by the transcriptional regulators Cap2/Hap43, the trimeric HAP complex, Sef1, and Sfu1 (reviewed in references 15 and 16 ). While the HAP complex, represented by the Hap5 subunit, is recruited to both induced as well as repressed gene promoters under iron-deficient conditions ( 6 ), Cap2 is recruited to the repressed promoters such as ACO1 and CYC1 , and Sef1 is recruited to induced promoters ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Multiple Evolutionarily Conserved Domains of Cap2 Are Required for Promoter Recruitment and Iron Homeostasis Gene Regulation

Srivastav

Agarwal

Natarajan

2018

mSphere

Self Cite

View full text Add to dashboard Cite

Iron is an essential micronutrient for living cells. Candida albicans, the predominant human fungal pathogen, thrives under diverse environments with vastly different iron levels in the mammalian host. Therefore, to tightly control iron homeostasis, C. albicans has evolved a set of transcriptional regulators that cooperate to either upregulate or downregulate transcription of iron uptake genes or iron utilization genes. Cap2/Hap43, a critical transcriptional regulator, contains multiple conserved protein domains. In this study, we carried out mutational analyses to identify the functional roles of the conserved protein domains in Cap2. Our results show that the bZIP, HAP4L, and the C-terminal domain are each required for Cap2 transcriptional activity. Thus, Cap2 employs multiple, disparate protein domains for regulation of iron homeostasis in C. albicans.

show abstract

“…As drug resistance is a major threat, there is an urgent need to identify new genes/pathways that are essential for the survival and pathogenicity of C. albicans . In addition to the essential genes, studies have shown that genes required for critical pathways, including iron homeostasis ( 2 , 3 ), ergosterol biosynthesis ( 4 ), and fatty acid biosynthesis ( 5 ), are also known to be important for survival in the host.…”

Section: Introductionmentioning

confidence: 99%

A CUG codon-adapted anchor-away toolkit for functional analysis of genes in Candida albicans

Teli,

Nagar,

Priyadarshini

et al. 2024

mSphere

Self Cite

View full text Add to dashboard Cite

Promoter shutoff of essential genes in the diploid Candida albicans has often been insufficient to create tight, conditional null alleles due to leaky expression and has been a stumbling block in pathogenesis research. Moreover, homozygous deletion of non-essential genes has often been problematic due to the frequent aneuploidy in the mutant strains. Rapid, conditional depletion of essential genes by the anchor-away strategy has been successfully employed in Saccharomyces cerevisiae and other model organisms. Here, rapamycin mediates the dimerization of human FK506-binding protein (FKBP12) and FKBP12-rapamycin-binding (FRB) domain-containing target protein, resulting in relocalization to altered sub-cellular locations. In this work, we used the ribosomal protein Rpl13 as the anchor and took two nuclear proteins as targets to construct a set of mutants in a proof-of-principle approach. We first constructed a rapamycin-resistant C. albicans strain by introducing a dominant mutation in the CaTOR1 gene and a homozygous deletion of RBP1 , the ortholog of FKBP12 , a primary target of rapamycin. The FKBP12 and the FRB coding sequences were then CUG codon-adapted for C. albicans by site-directed mutagenesis. Anchor-away strains expressing the essential TBP1 gene or the non-essential SPT8 gene as FRB fusions were constructed. We found that rapamycin caused rapid cessation of growth of the TBP-AA strain within 15 minutes and the SPT8-AA strain phenocopied the constitutive filamentous phenotype of the spt8 Δ/ spt8 Δ mutant. Thus, the anchor-away toolbox for C. albicans developed here can be employed for genome-wide analysis to identify gene function in a rapid and reliable manner, further accelerating anti-fungal drug development in C. albicans . IMPORTANCE Molecular genetic studies thus far have identified ~27% open-reading frames as being essential for the vegetative growth of Candida albicans in rich medium out of a total 6,198 haploid set of open reading frames. However, a major limitation has been to construct rapid conditional alleles of essential C. albicans genes with near quantitative depletion of encoded proteins. Here, we have developed a toolbox for rapid and conditional depletion of genes that would aid studies of gene function of both essential and non-essential genes.

show abstract

Iron Acquisition in the Pathobiology of Candida albicans

Cited by 3 publications

References 110 publications

Interplay between transcriptional regulators and the SAGA chromatin modifying complex fine-tune iron homeostasis

Interplay between transcriptional regulators and the SAGA chromatin modifying complex fine-tune iron homeostasis

Multiple Evolutionarily Conserved Domains of Cap2 Are Required for Promoter Recruitment and Iron Homeostasis Gene Regulation

A CUG codon-adapted anchor-away toolkit for functional analysis of genes in Candida albicans

Contact Info

Product

Resources

About