The Marine Sponge-Derived Polyketide Endoperoxide Plakortide F Acid Mediates Its Antifungal Activity by Interfering with Calcium Homeostasis

Xu, Tao; Feng, Qin; Jacob, Melissa R.; Avula, Bharathi; Mask, Melanie M.; Baerson, Scott R.; Tripathi, Siddharth; Mohammed, Rabab; Hamann, Mark T.; Khan, Ikhlas A.; Walker, Larry; Clark, Alice M.; Agarwal, Ameeta K.

doi:10.1128/aac.01022-10

Cited by 32 publications

(44 citation statements)

References 36 publications

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“…Another marine-derived polyketide, endoperoxide plakortide F acid (PFA), was found to elicit a transcriptomic response indicative of a Ca 2ϩ imbalance. This response affected the expression of genes known to be responsive to altered cellular calcium levels and strongly inhibited the opportunistic fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus (107). The authors showed that calcium transporters, including those with pmr1/pmr1 and pmc1/pmc1 mutations, were sensitive to PFA, and this finding agreed with the transcriptional response to PFA, which appears to be indicative of Ca 2ϩ overload-related stress.…”

Section: Interference With the Calcium Secretory System On The Endomesupporting

confidence: 77%

Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

et al. 2015

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dIn recent years, the emergence of fungal resistance has become frequent, partly due to the widespread clinical use of fluconazole, which is minimally toxic and effective in the prevention and treatment of Candida albicans infections. The limited selection of antifungal drugs for clinical fungal infection therapy has prompted us to search for new antifungal drug targets. Calcium, which acts as the second messenger in both mammals and fungi, plays a direct role in controlling the expression patterns of its signaling systems and has important roles in cell survival. In addition, calcium and some of the components, mainly calcineurin, in the fungal calcium signaling pathway mediate fungal resistance to antifungal drugs. Therefore, an overview of the components of the fungal calcium-calcineurin signaling network and their potential roles as antifungal targets is urgently needed. The calciumcalcineurin signaling pathway consists of various channels, transporters, pumps, and other proteins or enzymes. Many transcriptional profiles have indicated that mutant strains that lack some of these components are sensitized to fluconazole or other antifungal drugs. In addition, many researchers have identified efficient compounds that exhibit antifungal activity by themselves or in combination with antifungal drugs by targeting some of the components in the fungal calcium-calcineurin signaling pathway. This targeting disrupts Ca 2؉ homeostasis, which suggests that this pathway contains potential targets for the development of new antifungal drugs.

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Section: Interference With the Calcium Secretory System On The Endomesupporting

confidence: 77%

Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

et al. 2015

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“…Similarly, the mechanism of antifungal action involves permeabilization of the fungal membrane (Sionov et al 2005; Wong et al 2012). However, the mechanism has been studied in only a few cases (Shi et al 2012; Sionov et al 2005; Xu et al 2011b). A variety of viruses including herpes simplex virus, fish nodavirus, fish nodavirus, influenza virus A and B, respiratory syndrome virus, porcine reproductive virus, tobacco mosaic virus, human metapneumovirus, human immunodeficiency virus, hepatitis C virus, herpes simplex virus, human cytomegalovirus, and white spot syndrome virus are produced by bacteria, fungi, algae, cnidarians, crustaceans, echinoderms, tunicates, and fish.…”

Section: Discussionmentioning

confidence: 99%

“…Plakortide F acid induced transcription of a lacZ reporter gene activated by the calcineurin-dependent response element. A rise in intracellular calcium levels occurred in response to plakortide F acid (Xu et al 2011b). …”

Section: Antifungal Productsmentioning

confidence: 99%

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Antifungal and antiviral products of marine organisms

Cheung

Wong

Pan

et al. 2014

Appl Microbiol Biotechnol

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Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (−)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (−)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1–5 (TH 1–5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the afore-mentioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of employing them in clinical practice are promising in view of the wealth of these compounds from marine organisms. The compounds may also be used in agriculture and the food industry.

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“…These sets were chosen since they are well studies and the relative simplicity in having a control set and an experimental set; they were downloaded from the Gene Expression Omnibus on September 12, 2014. The series are: GSE 10073, which measures yeast gene expression in the presence of sampangine, and alkaloid [17]; GSE 26925, which measures the effects of plafortide F acid [18]; and GSE 7820, which measures two different strains of yeast under rich and nitrogendeficient conditions [19].…”

Section: Methodsmentioning

confidence: 99%

On the impact of data integration and edge enrichment in mining significant signals from biological networks

West

Ali

2014

Proceedings of the 5th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics

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The influx of high-throughput biotechnologies has resulted in considerable amounts of available and untapped data, useful for both interpretation and extrapolation. Due to the fact that the noise to signal ratio in most biological databases are non-trivial, single source analysis techniques may suffer from relatively high falsepositive and false-negative rates. In addition, use of a single data source does not allow for the discovery of the novel relationships that can only be derived from multiple sources. Recently, the use of gene correlation networks has emerged to assist in the discovery of previously unknown genetic relationships and the identification of significant biological functions. Such networks provide a useful mechanism to model experimental results obtained from expression data and capture a snapshot of the expression as well as the temporal changes in various experiments. In addition, gene Ontology is often integrated with biological networks within the analysis process as a source of domain knowledge. In this project, we evaluate the use of Gene Ontology, not simply as an assessment tool, but as a basic component in building the correlation networks. We implemented a network integration algorithm that uses both gene expression data (experimental knowledge) and gene ontology data (domain knowledge) to build a biologically-rich correlation model. Then, we analyzed the resulting networks for topological changes and biological significance changes. Our main hypothesis is that the integrated networks would reduce the harmful effects of outliers from imperfect data while maintaining the high concentration of network substructures that are likely to reveal novel, biologically-significant relationships. In addition, using the concept of "guilt by association", we analyzed the clusters of the integrated networks and found that there was a significant increase of enrichment scores relative to the original networks. We show, through motif and pathway analysis, that integrated networks tend to cluster with higher biological significance.

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The Marine Sponge-Derived Polyketide Endoperoxide Plakortide F Acid Mediates Its Antifungal Activity by Interfering with Calcium Homeostasis

Cited by 32 publications

References 36 publications

Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

Antifungal and antiviral products of marine organisms

On the impact of data integration and edge enrichment in mining significant signals from biological networks

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