L-687, 781, a new member of the papulacandin family of .BETA.-1,3-d-glucan synthesis inhibitors. I. Fermentation, isolation, and biological activity.

Vanmiddlesworth, Frank; Omstead, Mary Nallin; Schmatz, Dennis M.; Bartizal, Ken; Fromtling, Robert A.; Bills, Gerald F.; Nollstadt, K; Honeycutt, Susan S.; Zweerink, Marcia; Wilson, Ken

doi:10.7164/antibiotics.44.45

Cited by 48 publications

(22 citation statements)

References 13 publications

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“…Recent studies have also demonstrated the potential clinical usefulness of ␤-glucan as potential marker for pneumocystis pneumonia (PcP) in serum and bronchoalveolar lavage fluid (BALF) (19)(20)(21)(22)(23)(24)(25). Inhibition of Pneumocystis ␤-glucan synthase may provide, in part, an alternative treatment option for patients with PcP (2,7,(27)(28)(29)(30)(31).…”

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Characterization of a Distinct Host Response Profile to Pneumocystismurina Asci during Clearance of Pneumocystis Pneumonia

et al. 2013

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؉ T cell influx and expression of macrophage inflammatory response markers. A more robust cellular response was also observed in the untreated mice, with increased numbers of macrophages and neutrophils that were associated with greater lung damage. Markers of a Th17 response were also elevated in the untreated mice. These results suggest that the host mounts unique responses to asci and trophic forms. That these 2 life cycle stages provoked distinct host response profiles has significant implications for clearance and interpretation of the host immune responses to PcP.

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Characterization of a Distinct Host Response Profile to Pneumocystismurina Asci during Clearance of Pneumocystis Pneumonia

et al. 2013

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“…In Saccharomyces cerevisiae, GS consists of at least two subunits: a putative catalytic subunit encoded by related genes FKS1 and FKS2 (7,10) and a regulatory subunit, a GTP-bound protein encoded by RHO1 (16). Several types of GS inhibitors, such as echinocandins (5,13), papulacandins (20), and FR901469 (8), have been identified. GS inhibitors are a new class of antifungal antibiotics with clinical significance because of their strong fungicidal activity and low toxicity (1,3).…”

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FKS1 Mutations Responsible for Selective Resistance of Saccharomyces cerevisiae to the Novel 1,3-β-Glucan Synthase Inhibitor Arborcandin C

Ohyama¹,

Miyakoshi²,

Isono³

2004

Antimicrob Agents Chemother

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“…Nikkomycins and polyoxins are competitive inhibitors of chitin synthases (7,10,11,18). Papulacandin B (2,30,43,48), aculeacin A (29,49), echinocandin B (46), and pneumocandin B 0 (6) inhibit synthesis of 1,3-␤-glucan, most likely by inhibiting activity of 1,3-␤-glucan synthase. The killer toxin of Hansenula mrakii kills sensitive strains of S. cerevisiae by inhibiting 1,3-␤-glucan synthase activity (25,50).…”

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Cloning and characterization of GNS1: a Saccharomyces cerevisiae gene involved in synthesis of 1,3-beta-glucan in vitro

El-Sherbeini

Clemas

1995

J Bacteriol

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The GNS1 gene product is required for the synthesis of 1,3-␤-glucan in vitro, since mutations in this gene result in exhibit an 80 to 90% reduction in 1,3-␤-glucan synthase specific activity. gns1 mutant strains display a pleiotropic phenotype including resistance to a pneumocandin B 0 analog (L-733,560), slow growth, and mating and sporulation defects. The gns1-1 mutation was genetically mapped to within 1.35 centimorgans from the MAT locus on chromosome III. The wild-type GNS1 gene was isolated by complementing the pneumocandin resistance phenotype of the gns1-1 mutation and by hybridization with a chromosome III-derived sequence being used as a probe. The nucleotide sequence of GNS1 was determined and compared with the homologous region of the chromosome. The genetic and nucleotide sequence analyses revealed that GNS1 and the open reading frame, YCR34 [S. Oliver, Q. van der Aart, M. Agostoni-Carbone, and the Chromosome III Sequencing Group, Nature (London) 357:38-46, 1992], represent identical loci in the genome. Cells deleted for GNS1 are viable but exhibit slow growth as well as the pleiotropic phenotype of the gns1 mutants. The putative protein product is predicted to be an integral membrane protein with five transmembrane helices displaying an exoplasmic orientation for the N terminus and a cytoplasmic orientation for the C terminus. This protein may be a subunit of 1,3-␤-glucan synthase.

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L-687, 781, a new member of the papulacandin family of .BETA.-1,3-d-glucan synthesis inhibitors. I. Fermentation, isolation, and biological activity.

Abstract: A new /M,3-D-glucan synthesis inhibitor, L-687,781 is produced by the cultivation of Dictyochaeta simplex ATCC20960. L-687,781 exhibits potent in vitro antifungal activity as well as anti-Pneumocystis activity in a rat model.

Cited by 48 publications

References 13 publications

Characterization of a Distinct Host Response Profile to Pneumocystismurina Asci during Clearance of Pneumocystis Pneumonia

Characterization of a Distinct Host Response Profile to Pneumocystismurina Asci during Clearance of Pneumocystis Pneumonia

FKS1 Mutations Responsible for Selective Resistance of Saccharomyces cerevisiae to the Novel 1,3-β-Glucan Synthase Inhibitor Arborcandin C

Cloning and characterization of GNS1: a Saccharomyces cerevisiae gene involved in synthesis of 1,3-beta-glucan in vitro

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