Holden Whitney M, Ebert Alexander R, Canning Peter F, Rollins-Smith Louise A
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
Appl Environ Microbiol. 2014 Jul;80(13):4034-41. doi: 10.1128/AEM.04171-13. Epub 2014 Apr 25.
Chytridiomycosis, an amphibian skin disease caused by the emerging fungal pathogen Batrachochytrium 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) against B. dendrobatidis. Both chloramphenicol and amphotericin B significantly reduced B. dendrobatidis infection in naturally infected southern leopard frogs (Rana [Lithobates] sphenocephala), although neither drug was capable of complete fungal clearance. Long-term exposure of R. sphenocephala to 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 multiple R. sphenocephala skin bacterial isolates in vitro at concentrations below the MIC against B. 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.
蛙壶菌病是一种由新出现的真菌病原体蛙壶菌引起的两栖动物皮肤病，与全球两栖动物灾难性的数量下降有关。其结果是两栖动物多样性惊人地减少，这引起了科学界的极大关注。需要进行临床试验来测试潜在的抗真菌药物，以确定针对感染这种病原体的两栖动物的替代治疗方法。在本研究中，我们测定了氯霉素（800μg/ml）、两性霉素B（0.8至1.6μg/ml）和伊曲康唑（斯皮仁诺）（20ng/ml）对蛙壶菌的最低抑菌浓度（MIC）。氯霉素和两性霉素B均能显著降低自然感染的南方豹蛙（细趾蟾属[石蟾属]斯氏蛙）体内的蛙壶菌感染，尽管两种药物都不能完全清除真菌。长期将斯氏蛙暴露于这些药物中不会抑制抗菌肽（AMP）的合成，这表明这两种药物对这种重要的先天性皮肤防御均无损害。然而，我们观察到，氯霉素在低于其对蛙壶菌的MIC的浓度下，能在体外抑制多种斯氏蛙皮肤细菌分离株的生长，而两性霉素B和伊曲康唑则不能。这些结果表明，当氯霉素用作抗真菌剂时，可能会显著改变具有保护作用的天然皮肤微生物群。本研究首次考察了替代抗真菌药物治疗对两栖动物先天性皮肤防御的影响，这是验证这些治疗方法实际应用的关键一步。
