Effects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperature

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dc.creatorPaolo, William F.en
dc.creatorDadachova, Ekaterinaen
dc.creatorMandal, Piyalien
dc.creatorCasadevall, Arturoen
dc.creatorSzaniszlo, Paul J.en
dc.creatorNosanchuk, Joshua D.en
dc.date.accessioned2014-12-15T17:10:28Zen
dc.date.available2014-12-15T17:10:28Zen
dc.date.issued2006-06-19en
dc.descriptionWilliam F. Paolo Jr., Arturo Casadevall, and Joshua D. Nosanchuk are with the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA -- Ekaterina Dadachova, Piyali Mandal, Arturo Casadevall, and Joshua D. Nosanchuk are with the Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA -- Ekaterina Dadachova is with the Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, NY, USA -- Piyali Mandal is with the Department of Microbiology, All India Institute of Medical Sciences and Division of Infectious Diseases, New Delhi, India -- Paul J. Szaniszlo is with the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX, USA -- 6 Department of Medicine, New York University Medical Center, NY, USAen
dc.description.abstractBackground: Wangiella dermatitidis is a human pathogenic fungus that is an etiologic agent of phaeohyphomycosis. W. dermatitidis produces a black pigment that has been identified as a dihydroxynaphthalene melanin and the production of this pigment is associated with its virulence. Cell wall pigmentation in W. dermatitidis depends on the WdPKS1 gene, which encodes a polyketide synthase required for generating the key precursor for dihydroxynaphthalene melanin biosynthesis. -- Results: We analyzed the effects of disrupting WdPKS1 on dihydroxynaphthalene melanin production and resistance to antifungal compounds. Transmission electron microscopy revealed that wdpks1Δ-1 yeast had thinner cell walls that lacked an electron-opaque layer compared to wild-type cells. However, digestion of the wdpks1Δ-1 yeast revealed small black particles that were consistent with a melanin-like compound, because they were acid-resistant, reacted with melanin-binding antibody, and demonstrated a free radical signature by electron spin resonance analysis. Despite lacking the WdPKS1 gene, the mutant yeast were capable of catalyzing the formation of melanin from L-3,4-dihyroxyphenylalanine. The wdpks1Δ-1 cells were significantly more susceptible to killing by voriconazole, amphotericin B, NP-1 [a microbicidal peptide], heat and cold, and lysing enzymes than the heavily melanized parental or complemented strains. -- Conclusion: In summary, W. dermatitidis makes WdPKS-dependent and -independent melanins, and the WdPKS1-dependent deposition of melanin in the cell wall confers protection against antifungal agents and environmental stresses. The biological role of the WdPKS-independent melanin remains unclear.en
dc.description.catalogingnotenosanchu@aecom.yu.eduen
dc.description.departmentMolecular Biosciencesen
dc.description.sponsorshipen
dc.identifier.Filename1471-2180-6-55en
dc.identifier.citationPaolo, William F., Ekaterina Dadachova, Piyali Mandal, Arturo Casadevall, Paul J. Szaniszlo, and Joshua D. Nosanchuk. “Effects of Disrupting the Polyketide Synthase Gene WdPKS1 in Wangiella [Exophiala] Dermatitidis on Melanin Production and Resistance to Killing by Antifungal Compounds, Enzymatic Degradation, and Extremes in Temperature.” BMC Microbiology 6, no. 1 (June 19, 2006): 55. doi:10.1186/1471-2180-6-55.en
dc.identifier.doidoi:10.1186/1471-2180-6-55en
dc.identifier.urihttp://hdl.handle.net/2152/27886en
dc.language.isoEnglishen
dc.publisherBMC Microbiologyen
dc.rightsAdministrative deposit of works to UT Digital Repository: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access at http://www.biomedcentral.com. The public license is specified as CC-BY: http://creativecommons.org/licenses/by/4.0/. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en
dc.subjectWdPKS1en
dc.subjectWangiella dermatitidisen
dc.subjecthuman pathogenic fungusen
dc.subjectdihydroxynaphthalene melaninen
dc.titleEffects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperatureen
dc.typeArticleen

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