Isolation, structure and biological activity of phomafungin, a cyclic lipodepsipeptide from a widespread tropical Phoma sp.

Herath, Kithsiri; Harris, Guy H.; Jayasuriya, Hiranthi; Zink, Deborah L.; Smith, Scott K.; Vicente, Francisca; Bills, Gerald F.; Collado, Javier; González, Antonio; Jiang, Bo; Kahn, Jennifer Nielsen; Galuska, Stefan; Giacobbe, Robert A.; Abruzzo, George K.; Hickey, Emily; Liberator, Paul; Xu, Deming; Roemer, Terry; Singh, Sheo B.

doi:10.1016/j.bmc.2008.12.009

Cited by 42 publications

(45 citation statements)

References 36 publications

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“…In most cases the fitness test profiles are highly indicative of the biological activities of the compounds tested, as the hypersensitive and resistant strains reveal aspects of MOAs of antiproliferative compounds that are susceptible to a 50% loss of gene dosage. Indeed, CaFT profiling was used to determine the MOAs of novel antifungal synthetic compounds (9,10) and natural products (11)(12)(13). In this report we present the identification of structurally related small-molecule inhibitors that elicited significant hypersensitivity of the OLE1 ϩ/Ϫ strain in the fitness test and demonstrate that the two selected compounds reduce the level of unsaturated fatty acids and block hyphal growth.…”

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confidence: 89%

Chemical Genetic Profiling and Characterization of Small-molecule Compounds That Affect the Biosynthesis of Unsaturated Fatty Acids in Candida albicans

Sillaots

Davison

et al. 2009

Journal of Biological Chemistry

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The balance between saturated and unsaturated fatty acids plays a crucial role in determining the membrane fluidity. In the diploid fungal pathogen Candida albicans, the gene for fatty acid ⌬9 desaturase, OLE1, is essential for viability. Using a reverse genetic approach, termed the fitness test, we identified a group of structurally related synthetic compounds that induce specific hypersensitivity of the OLE1

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confidence: 89%

Chemical Genetic Profiling and Characterization of Small-molecule Compounds That Affect the Biosynthesis of Unsaturated Fatty Acids in Candida albicans

Sillaots

Davison

et al. 2009

Journal of Biological Chemistry

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“…Next, we compared the data of the RsAFP2 CaFT with CaFT data obtained with other antifungal compounds that affect sphingolipid/ceramide biosynthesis (Fig. 1B), namely the mycotoxins lipoxamycins and fumonisin and the cyclic lipodepsipeptide phomafungin (Mandala et al ., 1994; Cowart and Obeid, 2007; Herath et al ., 2009). The CaFT profiles of these antifungal compounds were distinct from that of RsAFP2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans

Thevissen

Tavares

et al. 2012

Molecular Microbiology

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Summary The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2,868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes was involved in cell wall integrity and hyphal growth/septin ring formation. Consistent with these genetic data, we demonstrated that RsAFP2 interacts with the cell wall of C. albicans, which also contains glucosylceramides, and activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces mislocalization of septins and blocks the yeast-to-hypha transition in C. albicans. Increased ceramide levels have previously been shown to result in apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans membranes were analyzed following RsAFP2 treatment and, as expected, increased accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans cells was detected. This is the first report on the interaction of a plant defensin with glucosylceramides in the fungal cell wall, causing cell wall stress, and on the effects of a defensin on septin localization and ceramide accumulation.

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“…[51][52][53][54] 11.4 Discovery of New Antibacterial Compounds 11.4.1 Antibacterial Compounds Derived from the Target-based Antisense-Sensitized S. aureus Screening…”

Section: Novel Approaches To Exploit Natural Products From Microbial mentioning

confidence: 99%

Chapter 11. Novel Approaches to Exploit Natural Products from Microbial Resources

Genilloud¹,

Vicente²

2012

Drug Discovery

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Isolation, structure and biological activity of phomafungin, a cyclic lipodepsipeptide from a widespread tropical Phoma sp.

Cited by 42 publications

References 36 publications

Chemical Genetic Profiling and Characterization of Small-molecule Compounds That Affect the Biosynthesis of Unsaturated Fatty Acids in Candida albicans

Chemical Genetic Profiling and Characterization of Small-molecule Compounds That Affect the Biosynthesis of Unsaturated Fatty Acids in Candida albicans

The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans

Chapter 11. Novel Approaches to Exploit Natural Products from Microbial Resources

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