Functions of CaPhm7 in the regulation of ion homeostasis, drug tolerance, filamentation and virulence in Candida albicans

Jiang, Lijing; Pan, Hongbo

doi:10.1186/s12866-018-1193-9

Cited by 16 publications

(14 citation statements)

References 39 publications

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“…The Phm7 protein sequence contains several transmembrane domains [54], and the protein is localized in the plasma membrane [55]. Its ortholog CaPhm7 in Candida albicans is also localized in the plasma membrane, and participates in drug resistance and filamentous growth [56,57]. The cells lacking CaPHM7 are sensitive to SDS and ketoconazole, but resistant to rapamycin and zinc [56].…”

Section: Discussionmentioning

confidence: 99%

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The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in Saccharomyces cerevisiae

Trilisenko

Zvonarev

Valiakhmetov

et al. 2019

Cells

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Inorganic polyphosphate (polyP) is crucial for adaptive reactions and stress response in microorganisms. A convenient model to study the role of polyP in yeast is the Saccharomyces cerevisiae strain CRN/PPN1 that overexpresses polyphosphatase Ppn1 with stably decreased polyphosphate level. In this study, we combined the whole-transcriptome sequencing, fluorescence microscopy, and polyP quantification to characterize the CRN/PPN1 response to manganese and oxidative stresses. CRN/PPN1 exhibits enhanced resistance to manganese and peroxide due to its pre-adaptive state observed in normal conditions. The pre-adaptive state is characterized by up-regulated genes involved in response to an external stimulus, plasma membrane organization, and oxidation/reduction. The transcriptome-wide data allowed the identification of particular genes crucial for overcoming the manganese excess. The key gene responsible for manganese resistance is PHO84 encoding a low-affinity manganese transporter: Strong PHO84 down-regulation in CRN/PPN1 increases manganese resistance by reduced manganese uptake. On the contrary, PHM7, the top up-regulated gene in CRN/PPN1, is also strongly up-regulated in the manganese-adapted parent strain. Phm7 is an unannotated protein, but manganese adaptation is significantly impaired in Δphm7, thus suggesting its essential function in manganese or phosphate transport.

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Section: Discussionmentioning

confidence: 99%

“…Its ortholog CaPhm7 in Candida albicans is also localized in the plasma membrane, and participates in drug resistance and filamentous growth [56,57]. The cells lacking CaPHM7 are sensitive to SDS and ketoconazole, but resistant to rapamycin and zinc [56]. This evidence suggests that Phm7 is a membrane transporter of divalent metal cations.…”

Section: Discussionmentioning

confidence: 99%

The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in Saccharomyces cerevisiae

Trilisenko

Zvonarev

Valiakhmetov

et al. 2019

Cells

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“…The other gene in these intervals ( MKT1 ) has an unclear function. Notably, ADH1 51 , MKT1 52 , and PHM7 53 have been found to affect pathogenicity in other fungi, and both endosomal function 54 and thiamine transport 55 have been linked to virulence as well. Our system provides an opportunity not only to identify new mechanisms underlying persistence in hosts, but also to study how both known and unknown mechanisms act in combination.…”

Section: Discussionmentioning

confidence: 99%

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body

Mullis

Ghione

Lough-Stevens

et al. 2022

Preprint

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Determining how genetic polymorphisms enable certain fungi to persist in mammalian hosts can improve understanding of opportunistic fungal pathogenesis, a source of substantial human morbidity and mortality. We examined the genetic basis of fungal persistence in mice using a cross between a clinical isolate and the lab reference strain of the budding yeast Saccharomyces cerevisiae. Employing chromosomally-encoded barcodes, we tracked the relative abundances of 822 genotyped, haploid segregants in multiple organs over time and performed linkage mapping of their persistence in hosts. Detected loci showed a mix of general and antagonistically pleiotropic effects across organs. General loci showed similar effects across all organs, while antagonistically pleiotropic loci showed contrasting effects in the brain and the kidneys, liver, and spleen. Persistence in an organ required both generally beneficial alleles and organ-appropriate pleiotropic alleles. This genetic architecture resulted in many segregants persisting in the brain or in non-brain organs, but few segregants persisting in all organs. These results show complex combinations of genetic polymorphisms collectively cause and constrain fungal persistence in different parts of the mammalian body.

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“…In yeasts, they play roles in ion homeostasis, growth, filamentation and pathogenicity and have implications on the biosynthesis of signal molecules and bioactive metabolites [ 46 , 47 ]. These TRPs allow the translocation of calcium from the cytosol to calcium reservoirs by using the proton gradient in the plasma membrane and in membranes of intracellular organelles [ 48 ]. The increase in the basal cytoplasmic calcium level is due to a transient opening of the ion channel providing calcium influx from either the extracellular medium or from the calcium store organelles.…”

Section: Transient Receptor Potential Ion Channels In Fungal Metabolismmentioning

confidence: 99%

Vacuolal and Peroxisomal Calcium Ion Transporters in Yeasts and Fungi: Key Role in the Translocation of Intermediates in the Biosynthesis of Fungal Metabolites

Martı́n

2022

Genes

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The intracellular calcium content in fungal cells is influenced by a large number of environmental and nutritional factors. Sharp changes in the cytosolic calcium level act as signals that are decoded by the cell gene expression machinery, resulting in several physiological responses, including differentiation and secondary metabolites biosynthesis. Expression of the three penicillin biosynthetic genes is regulated by calcium ions, but there is still little information on the role of this ion in the translocation of penicillin intermediates between different subcellular compartments. Using advanced information on the transport of calcium in organelles in yeast as a model, this article reviews the recent progress on the transport of calcium in vacuoles and peroxisomes and its relation to the translocation of biosynthetic intermediates in filamentous fungi. The Penicillium chrysogenum PenV vacuole transporter and the Acremonium chrysogenum CefP peroxisomal transporter belong to the transient receptor potential (TRP) class CSC of calcium ion channels. The PenV transporter plays an important role in providing precursors for the biosynthesis of the tripeptide δ-(-α-aminoadipyl-L-cysteinyl-D-valine), the first intermediate of penicillin biosynthesis in P. chrysogenum. Similarly, CefP exerts a key function in the conversion of isopenicillin N to penicillin N in peroxisomes of A. chrysogenum. These TRP transporters are different from other TRP ion channels of Giberella zeae that belong to the Yvc1 class of yeast TRPs. Recent advances in filamentous fungi indicate that the cytosolic calcium concentration signal is connected to the calcitonin/calcineurin signal transduction cascade that controls the expression of genes involved in the subcellular translocation of intermediates during fungal metabolite biosynthesis. These advances open new possibilities to enhance the expression of important biosynthetic genes in fungi.

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Functions of CaPhm7 in the regulation of ion homeostasis, drug tolerance, filamentation and virulence in Candida albicans

Cited by 16 publications

References 39 publications

The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in Saccharomyces cerevisiae

The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in Saccharomyces cerevisiae

Complex genetics cause and constrain fungal persistence in different parts of the mammalian body

Vacuolal and Peroxisomal Calcium Ion Transporters in Yeasts and Fungi: Key Role in the Translocation of Intermediates in the Biosynthesis of Fungal Metabolites

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