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Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.

Publication ,  Journal Article
Perlatti, B; Harris, G; Nichols, CB; Ekanayake, DI; Alspaugh, JA; Gloer, JB; Bills, GF
Published in: J Nat Prod
September 25, 2020

Campafungin A is a polyketide that was recognized in the Candida albicans fitness test due to its antiproliferative and antihyphal activity. Its mode of action was hypothesized to involve inhibition of a cAMP-dependent PKA pathway. The originally proposed structure appeared to require a polyketide assembled in a somewhat unusual fashion. However, structural characterization data were never formally published. This background stimulated a reinvestigation in which campafungin A and three closely related minor constituents were purified from fermentations of a strain of the ascomycete fungus Plenodomus enteroleucus. Labeling studies, along with extensive NMR analysis, enabled assignment of a revised structure consistent with conventional polyketide synthetic machinery. The structure elucidation of campafungin A and new analogues encountered in this study, designated here as campafungins B, C, and D, is presented, along with a proposed biosynthetic route. The antimicrobial spectrum was expanded to methicillin-resistant Staphylococcus aureus, Candida tropicalis, Candida glabrata, Cryptococcus neoformans, Aspergillus fumigatus, and Schizosaccharomyces pombe, with MICs ranging as low as 4-8 μg mL-1 in C. neoformans. Mode-of-action studies employing libraries of C. neoformans mutants indicated that multiple pathways were affected, but mutants in PKA/cAMP pathways were unaffected, indicating that the mode of action was distinct from that observed in C. albicans.

Duke Scholars

Published In

J Nat Prod

DOI

EISSN

1520-6025

Publication Date

September 25, 2020

Volume

83

Issue

9

Start / End Page

2718 / 2726

Location

United States

Related Subject Headings

  • Signal Transduction
  • Polyketides
  • Molecular Structure
  • Microbial Sensitivity Tests
  • Medicinal & Biomolecular Chemistry
  • Hyphae
  • Fungi
  • Fermentation
  • Cyclic AMP-Dependent Protein Kinases
  • Cryptococcus neoformans
 

Citation

APA
Chicago
ICMJE
MLA
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Perlatti, B., Harris, G., Nichols, C. B., Ekanayake, D. I., Alspaugh, J. A., Gloer, J. B., & Bills, G. F. (2020). Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth. J Nat Prod, 83(9), 2718–2726. https://doi.org/10.1021/acs.jnatprod.0c00641
Perlatti, Bruno, Guy Harris, Connie B. Nichols, Dulamini I. Ekanayake, J Andrew Alspaugh, James B. Gloer, and Gerald F. Bills. “Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.J Nat Prod 83, no. 9 (September 25, 2020): 2718–26. https://doi.org/10.1021/acs.jnatprod.0c00641.
Perlatti B, Harris G, Nichols CB, Ekanayake DI, Alspaugh JA, Gloer JB, et al. Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth. J Nat Prod. 2020 Sep 25;83(9):2718–26.
Perlatti, Bruno, et al. “Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.J Nat Prod, vol. 83, no. 9, Sept. 2020, pp. 2718–26. Pubmed, doi:10.1021/acs.jnatprod.0c00641.
Perlatti B, Harris G, Nichols CB, Ekanayake DI, Alspaugh JA, Gloer JB, Bills GF. Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth. J Nat Prod. 2020 Sep 25;83(9):2718–2726.
Journal cover image

Published In

J Nat Prod

DOI

EISSN

1520-6025

Publication Date

September 25, 2020

Volume

83

Issue

9

Start / End Page

2718 / 2726

Location

United States

Related Subject Headings

  • Signal Transduction
  • Polyketides
  • Molecular Structure
  • Microbial Sensitivity Tests
  • Medicinal & Biomolecular Chemistry
  • Hyphae
  • Fungi
  • Fermentation
  • Cyclic AMP-Dependent Protein Kinases
  • Cryptococcus neoformans