title: Nikkomycin Z is an effective inhibitor of the chytrid fungus linked to global amphibian declines.
abstract: Fungal infections in humans, wildlife, and plants are a growing concern because of their devastating effects on human and ecosystem health. In recent years, populations of many amphibian species have declined, and some have become extinct due to chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis. For some endangered amphibian species, captive colonies are the best intermediate solution towards eventual reintroduction, and effective antifungal treatments are needed to cure chytridiomycosis and limit the spread of this pathogen in such survival assurance colonies. Currently, the best accepted treatment for infected amphibians is itraconazole, but its toxic side effects reduce its usefulness for many species. Safer antifungal treatments are needed for disease control. Here, we show that nikkomycin Z, a chitin synthase inhibitor, dramatically alters the cell wall stability of B. dendrobatidis cells and completely inhibits growth of B. dendrobatidis at 250 μM. Low doses of nikkomycin Z enhanced the effectiveness of natural antimicrobial skin peptide mixtures tested in vitro. These studies suggest that nikkomycin Z would be an effective treatment to significantly reduce the fungal burden in frogs infected by B. dendrobatidis.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: whitney.m.gammill@vanderbilt.edu.
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Holden
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. Electronic address: jeffrey.s.fites@vanderbilt.edu.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Fites
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: laura.reinert@vanderbilt.edu.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Reinert
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: louise.rollins-smith@vanderbilt.edu.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Rollins-Smith
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000663:Amphibians / Q000382:microbiology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects; D008411:Chytridiomycota / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000617:Aminoglycosides; D000935:Antifungal Agents; C011952:nikkomycin
keywords: Antifungal therapy; Antimicrobial peptides; B. dendrobatidis; BCA; Batrachochytrium dendrobatidis; Bd; Brevinin peptides; Chytridiomycosis; NZ; OD(490); bicinchoninic acid; m/z; mass to charge ratio; nikkomycin Z; optical density at λ = 490 nm