title: Antifungal thiopeptide cyclothiazomycin B1 exhibits growth inhibition accompanying morphological changes via binding to fungal cell wall chitin.
abstract: Cyclothiazomycin B1 (CTB1) is an antifungal cyclic thiopeptide isolated from the culture broth of Streptomyces sp. HA 125-40. CTB1 inhibited the growth of several filamentous fungi including plant pathogens along with swelling of hyphae and spores. The antifungal activity of CTB1 was weakened by hyperosmotic conditions, and hyphae treated with CTB1 burst under hypoosmotic conditions, indicating increased cell wall fragility. CTB1-sensitive fungal species contain high levels of cell wall chitin and/or chitosan. Unlike nikkomycin Z, a competitive inhibitor of chitin synthase (CHS), CTB1 did not inhibit CHS activity. Although CTB1 inhibited CHS biosynthesis, the same result was also obtained with a non-specific proteins inhibitor, cycloheximide, which did not reduce cell wall rigidity. These results indicate that the primary target of CTB1 is not CHS, and we concluded that CTB1 antifungal activity was independent of this sole inhibition. We found that CTB1 bound to chitin but did not bind to β-glucan and chitosan. The results of the present study suggest that CTB1 induces cell wall fragility by binding to chitin, which forms the fungal cell wall. The antifungal activity of CTB1 could be explained by this chitin-binding ability.
authors: Division of Molecular Materials Science, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors: Naoko
authors: N
authors: Mizuhara
authors: Manabu
authors: M
authors: Kuroda
authors: Akira
authors: A
authors: Ogita
authors: Toshio
authors: T
authors: Tanaka
authors: Yoshinosuke
authors: Y
authors: Usuki
authors: Ken-Ichi
authors: K
authors: Fujita
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects*; D002686:Chitin / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D041681:NIH 3T3 Cells; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000935:Antifungal Agents; D010455:Peptides; C569101:cyclothiazomycin B1; D002686:Chitin