Induction of Cell Wall Thickening by the Antifungal Compound Dihydromaltophilin Disrupts Fungal Growth and is Mediated by Sphingolipid Biosynthesis

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.