title: Induction of cell wall thickening by the antifungal compound dihydromaltophilin disrupts fungal growth and is mediated by sphingolipid biosynthesis.
abstract: Dihydromaltophilin (heat-stable antifungal factor [HSAF]) is an antifungal metabolite produced in Lysobacter enzymogenes biocontrol strain C3. This compound induces cell wall thickening in Aspergillus nidulans. Here we show that the cell wall thickening is a general response to HSAF in diverse fungal species. In the A. nidulans model, the thickened cell wall negatively affects hyphal growth. Growth of HSAF-pre-treated hyphae failed to resume at hyphal tips with thick cell wall and the actin cable could not re-polarize at the thickened region of the cell wall, even after the treated hyphae were transferred to drug-free medium. Moreover, HSAF-induced cell wall thickening is mediated by sphingolipid synthesis: HSAF failed to induce cell wall thickening in the absence of ceramide synthase BarA and the sphingolipid synthesis inhibitor myriocin was able to suppress HSAF-induced cell wall thickening. The thickened cell wall could be digested by chitinase suggesting that chitin contributes to the HSAF-induced thickening. Furthermore, HSAF treatment activated the transcription of two chitin synthase encoding genes chsB and chsC.
authors.affiliation: Department of Plant Pathology, University of Nebraska, Lincoln, Nebraska 68583, USA. shaojieli@gmail.com
authors.forename: Shaojie
authors.initials: S
authors.lastname: Li
authors.forename: Ana M
authors.initials: AM
authors.lastname: Calvo
authors.forename: Gary Y
authors.initials: GY
authors.lastname: Yuen
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Du
authors.forename: Steven D
authors.initials: SD
authors.lastname: Harris
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D001233:Aspergillus nidulans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism*; D002687:Chitin Synthase / Q000235:genetics / Q000378:metabolism; D002688:Chitinases / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D025301:Hyphae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007769:Lactams / Q000494:pharmacology*; D053528:Lysobacter / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D013107:Sphingolipids / Q000096:biosynthesis*
chemical_list: D000935:Antifungal Agents; D005229:Fatty Acids, Monounsaturated; D005656:Fungal Proteins; D007769:Lactams; D013107:Sphingolipids; C111136:dihydromaltophilin; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D002687:Chitin Synthase; D002688:Chitinases; C001996:thermozymocidin