Evaluation of Amphotericin B and Chloramphenicol as Alternative Drugs for Treatment of Chytridiomycosis and Their Impacts on Innate Skin Defenses
ABSTRACTChytridiomycosis, an amphibian skin disease caused by the emerging fungal pathogenBatrachochytrium dendrobatidis, has been implicated in catastrophic global amphibian declines. The result is an alarming decrease in amphibian diversity that is a great concern for the scientific community. Clinical trials testing potential antifungal drugs are needed to identify alternative treatments for amphibians infected with this pathogen. In this study, we quantified the MICs of chloramphenicol (800 μg/ml), amphotericin B (0.8 to 1.6 μg/ml), and itraconazole (Sporanox) (20 ng/ml) againstB. dendrobatidis. Both chloramphenicol and amphotericin B significantly reducedB. dendrobatidisinfection in naturally infected southern leopard frogs (Rana[Lithobates]sphenocephala), although neither drug was capable of complete fungal clearance. Long-term exposure ofR. sphenocephalato these drugs did not inhibit antimicrobial peptide (AMP) synthesis, indicating that neither drug is detrimental to this important innate skin defense. However, we observed that chloramphenicol, but not amphotericin B or itraconazole, inhibited the growth of multipleR. sphenocephalaskin bacterial isolatesin vitroat concentrations below the MIC againstB. dendrobatidis. These results indicate that treatment with chloramphenicol might dramatically alter the protective natural skin microbiome when used as an antifungal agent. This study represents the first examination of the effects of alternative antifungal drug treatments on amphibian innate skin defenses, a crucial step to validating these treatments for practical applications.