title: Radicinin from Cochliobolus sp. inhibits Xylella fastidiosa, the causal agent of Pierce's Disease of grapevine.
abstract: The fastidious phytopathogenic bacterium, Xylella fastidiosa, poses a substantial threat to many economically important crops, causing devastating diseases including Pierce's Disease of grapevine. Grapevines (Vitis vinifera L.) planted in an area under Pierce's Disease pressure often display differences in disease severity and symptom expression, with apparently healthy vines growing alongside the dying ones, despite the fact that all the vines are genetic clones of one another. Under the hypothesis that endophytic microbes might be responsible for this non-genetic resistance to X. fastidiosa, endophytic fungi were isolated from vineyard cvs. 'Chardonnay' and 'Cabernet Sauvignon' grown under high Pierce's Disease pressure. A Cochliobolus sp. isolated from a Cabernet Sauvignon grapevine inhibited the growth of X. fastidiosa in vitro. Bioassay-guided isolation of an organic extract of Cochliobolus sp. yielded the natural product radicinin as the major active compound. Radicinin also inhibited proteases isolated from the culture supernatant of X. fastidiosa. In order to assess structure-activity relationships, three semi-synthetic derivatives of radicinin were prepared and tested for activity against X. fastidiosa in vitro. Assay results of these derivatives are consistent with enzyme inactivation by conjugate addition to carbon-10 of radicinin, as proposed previously.
authors.affiliation: Department of Chemistry, Harvey Mudd College, Claremont, CA 91711, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Aldrich
authors.affiliation: Department of Botany and Plant Sciences, University of California, Riverside, CA 92521, USA.
authors.forename: Philippe E
authors.initials: PE
authors.lastname: Rolshausen
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, CA 92521, USA.
authors.forename: M Caroline
authors.initials: MC
authors.lastname: Roper
authors.affiliation: Department of Chemistry, Point Loma Nazarene University, 3900 Lomaland Drive, San Diego, CA 92106, USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Reader
authors.affiliation: Department of Chemistry, Point Loma Nazarene University, 3900 Lomaland Drive, San Diego, CA 92106, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Steinhaus
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, CA 92521, USA.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Rapicavoli
authors.affiliation: Department of Chemistry, Harvey Mudd College, Claremont, CA 91711, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Vosburg
authors.affiliation: Department of Chemistry, Harvey Mudd College, Claremont, CA 91711, USA; Department of Chemistry, Point Loma Nazarene University, 3900 Lomaland Drive, San Diego, CA 92106, USA. Electronic address: katherinemaloney@pointloma.edu.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Maloney
mesh_terms: D001203:Ascomycota / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010935:Plant Diseases / Q000382:microbiology; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D027843:Vitis / Q000382:microbiology*; D044167:Xylella / Q000187:drug effects*
chemical_list: D011753:Pyrones; C009157:radicinin
keywords: Antibiotic; Cochliobolus sp.; Endophytic fungus; Grapevine; Pierce’s Disease; Radicinin; Semisynthesis; Structure–activity relationships; Vitaceae; Vitis vinifera; Xylella fastidiosa