组蛋白-5 诱导酿酒酵母中 Pdr5p 介导的氟康唑耐药性的逆转。
Histatin-5 induces the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisae.
机构信息
Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco I-44, Cidade Universitária, 21941-590 Rio de Janeiro, RJ, Brazil.
Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco I-44, Cidade Universitária, 21941-590 Rio de Janeiro, RJ, Brazil.
出版信息
J Mycol Med. 2018 Mar;28(1):137-142. doi: 10.1016/j.mycmed.2017.11.002. Epub 2017 Dec 6.
BACKGROUND
Candidiasis is a major opportunistic fungal infection in humans. The low number of antifungal drugs available to treat Candida infections and the increasing incidence of multidrug resistant (MDR) strains point to an urgent need of identifying new therapeutic options. The role of salivary components can provide insights for the development of new methodologies of control.
OBJECTIVE
The aim of this study was to evaluate the ability of histatin-5, a constitutive immunological peptide present in saliva, in reversing fungal MDR phenotype, using a resistant Saccharomyces cerevisiae strain as model of study.
RESULTS
A total of 2.5μg and 5μg of histatin-5 revealed to be able to chemosensitize (to revert antifungal resistance) a MDR strain to fluconazole impairing its intrinsic resistance. The presence of histatin-5 decreased the strain growth when associated to fluconazole, and also assisted in the retention of rhodamine 6G within cell cytoplasm. The ATPase activity of Pdr5p, an ABC efflux transporter, was significantly reduced up to 65% within physiological concentration of the peptide.
CONCLUSION
Results revealed that histatin-5 is able to revert MDR phenotype and may be considered a potential alternative MDR inhibitor. Since Pdr5p is homologous to Candida albicans CaCdr1p and CaCdr2p, data obtained might be extrapolated to these transporters, inferring that associating fluconazole and histatin-5 may be a useful tool to circumvent failure treatments of infections caused by Candida MDR strains.
背景
念珠菌病是人类中一种主要的机会性真菌感染。可用于治疗念珠菌感染的抗真菌药物数量有限，且多药耐药（MDR）菌株的发病率不断上升，这表明迫切需要确定新的治疗选择。唾液成分的作用可以为开发新的控制方法提供思路。
目的
本研究旨在评估组织蛋白酶-5（一种存在于唾液中的固有免疫肽）逆转真菌 MDR 表型的能力，使用耐氟康唑的酿酒酵母作为研究模型。
结果
总共 2.5μg 和 5μg 的组织蛋白酶-5能够使 MDR 菌株对氟康唑产生化学敏感性（逆转抗真菌耐药性），从而削弱其固有耐药性。当与氟康唑联合使用时，组织蛋白酶-5的存在会抑制菌株的生长，并有助于将罗丹明 6G 保留在细胞质内。在生理浓度的肽存在下，Pdr5p（一种 ABC 外排转运蛋白）的 ATP 酶活性显著降低了 65%。
结论
结果表明，组织蛋白酶-5能够逆转 MDR 表型，可被视为一种潜在的 MDR 抑制剂。由于 Pdr5p 与白色念珠菌 CaCdr1p 和 CaCdr2p 同源，因此获得的数据可能会外推到这些转运蛋白，推断联合使用氟康唑和组织蛋白酶-5可能是规避由 MDR 念珠菌菌株引起的感染治疗失败的有用工具。
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