1. Occurrence and characterization of Colletotrichum dematium (Fr.) grove
Zofia Machowicz-Stefaniak Pol J Microbiol. 2010;59(3):191-200.
Colletotrichum dematium was isolated from caraway for the first time in Poland in 2005. Isolations of this fungus were repeated in 2006 and 2007. The cultures of fungus were obtained from superficially disinfected leaves, root necks, roots, stems and umbels. The isolates were identified on culture media: PDA and malt agar with addition of pieces of caraway stems and on the base of macro and microscopic structures. Studies on the biotic effect between C. dematium and other species of phyllosphere fungi of caraway showed that the majority of the studied species limited the growth and development of C. dematium, but the size of the limiting effect was different. The species from Trichoderma and Gliocladium genera were the most effective against C. dematium, causing degeneration and lysis of hyphae and precluded the formation of the pathogen's acervuli and conidia. C. dematium in dual culture with E. purpurascens, A. radicina, S. sclerotiorum, B. cinerea and R. solani produced an inhibition zone which indicated its capacity for antibiosis.
2. Cryptocandin, a potent antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina
Gary A Strobel, R Vincent Miller, Concepcion Martinez-Miller, Margaret M Condron, David B Teplow, W M Hess Microbiology (Reading). 1999 Aug;145 ( Pt 8):1919-1926. doi: 10.1099/13500872-145-8-1919.
A unique lipopeptide antimycotic, termed cryptocandin, is described from Cryptosporiopsis cf. quercina, an endophytic fungus. Cryptocandin, with a molecular mass of 1079 Da, contains equimolar amounts of 3,4-dihydroxyhomotyrosine, 4-hydroxyproline, threonine, glutamine, 3-hydroxy-4-hydroxymethylproline, 4,5-dihydroxyornithine and palmitic acid. Cryptocandin is chemically related to well-known antimycotics, the echinocandins and pneumocandins, which are produced by such fungi as Zalerion arboricola, Pezicula spp. and Aspergillus spp. Cryptocandin has minimal inhibitory concentration values of 0.03-0.07 microgram ml-1 against isolates of Candida albicans, Trichophyton mentagrophytes and Trichophyton rubrum. Cryptocandin is also active against a number of plant-pathogenic fungi including Sclerotinia sclerotiorum and Botrytis cinerea.
3. Cyclosporins: structure-activity relationships for the inhibition of the human FPR1 formylpeptide receptor
Francis Loor, Françoise Tiberghien, Tom Wenandy, Agnès Didier, Rene Traber J Med Chem. 2002 Oct 10;45(21):4613-28. doi: 10.1021/jm010987v.
The human formylpeptide receptor (FPR) is a seven-transmembranous G-protein-coupled receptor (7TM-GPCR) for chemotactic peptides of bacterial origins, possibly involved in the recruitment and activation of neutrophils in various inflammatory diseases of mucosal epithelia. Mutational analyses suggest that interactions of formylated peptides with FPR occur on the outer exoplasmic leaflet/domains of the plasma membrane. The immunosuppressive and antifungal antibiotic cyclic undecapeptide cyclosporin A (CsA; cyclo-[MeBmt(1)-Abu(2)-MeGly(3)-MeLeu(4)-Val(5)-MeLeu(6)-Ala(7)-D-Ala(8)-MeLeu(9)-MeLeu(10)-MeVal(11)]) and some tested analogues such as [Ala(2)]-CsA, [Thr(2)]-CsA, [Val(2)]-CsA, and [Nva(2)]-CsA were able of inhibiting the binding of formylpeptides to the FPR, with [D-MeVal(11)]-CsA (CsH) being much more active than the other analogues. CsH is devoid of immunosuppressive and antifungal activities, and its large potency for human FPR inhibition is of inverse agonism origin. Formylpeptide binding to FPR-expressing cells does not only induce chemotaxis; it also causes a rapid release of granule enzymes in the extracellular medium, allowing the easy monitoring of any inhibition of FPR function "in vivo" (with intact live cells). With such an assay, CsH was confirmed to be the most potent FPR inhibitory cyclosporin, although a far related immunosuppressive cyclosporin analogue, FR901459 ([Thr(2), Leu(5), Leu(10)]-CsA), was found to display a high FPR inhibitory activity (FPR-InhA). To establish structure-activity relationships (SAR) for FPR function inhibition, 59 cyclosporins were now studied by this standardized assay (with differentiated human leukemic cell line HL-60 as FPR-expressing cells and with N-acetyl-beta-D-glucosaminidase release as read-out). These SAR confirmed the low FPR-InhA of classical cyclosporins, where such activity was only seldom found: the most active ones ([Thr(2), Ile(5)]-CsA, [aMeIle(11)]-CsA, and [MeAla(11)]-CsA) remained 3-10-fold less potent than CsH. In contrast, the SAR disclosed that N(10)-desmethylated cyclosporins were particularly prone to display a large FPR-InhA: their most potent one was a [Thr(2), Gly(3), Leu(5), D-Hiv(8), Leu(10)]-CsA, found to be only 2-4-fold less active than [D-MeVal(11)]-CsA (CsH), with which it shows six differences out of 11 residues. Because the free conformations of both CsH and N(10)-desmethylated cyclosporins differ from those of "classical" (N(10)-methylated, [L-MeVal(11)]-using) cyclosporins, these potent FPR inhibitory cyclosporins probably bind to FPR pharmacophores for which classical cyclosporins show little affinity. Moreover, because the conformations of the N(10)-desmethylated cyclosporins widely differ from the CsH one, they probably bind to different pharmacophores on the FPR molecules.
