Kolaczkowski Marcin, Kolaczkowska Anna, Sroda Kamila, Ramalhete Cátia, Michalak Krystyna, Mulhovo Silva, Ferreira Maria José U
Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland.
Mycoses. 2010 Jul;53(4):305-10. doi: 10.1111/j.1439-0507.2009.01711.x. Epub 2009 May 13.
The effective treatment of infections caused by the most frequent human fungal pathogens Candida albicans and Candida glabrata is hindered by a limited number of available antifungals and development of resistance. In this study, we identified new extracts of medicinal plants inhibiting the growth of C. glabrata, a species generally showing low sensitivity to azoles. The methanolic extract of Anacardium occidentalis with an MIC of 80 microg ml(-1) proved to be the most active. In contrast to higher azole sensitivity, C. albicans showed increased resistance to several extracts. Investigation of the possible contribution of the multidrug transporter of the ATP-binding cassette superfamily Cdr1p of C. albicans to extract tolerance revealed a differential response upon overproduction of this protein in Saccharaomyces cerevisiae. Whereas the growth inhibitory activity of many extracts was not affected by CDR1 overexpression, increased sensitivity to some of them was observed. In contrast, extracts showing no detectable anticandidal activity including the ethyl acetate extract of Trichilia emetica were detoxified by Cdr1p. The presence of a non-toxic Cdr1p-mediated ketoconazole resistance modulator accompanying growth-inhibitory Cdr1p substrates in this extract was revealed by further fractionation experiments.
由最常见的人类真菌病原体白色念珠菌和光滑念珠菌引起的感染，其有效治疗受到可用抗真菌药物数量有限以及耐药性发展的阻碍。在本研究中，我们鉴定出了抑制光滑念珠菌生长的药用植物新提取物，该菌种通常对唑类药物敏感性较低。腰果的甲醇提取物最低抑菌浓度为80微克/毫升，被证明是活性最强的。与对唑类药物较高的敏感性不同，白色念珠菌对几种提取物表现出更高的耐药性。对白色念珠菌ATP结合盒超家族多药转运蛋白Cdr1p在提取物耐受性中可能作用的研究表明，在酿酒酵母中过量表达该蛋白时会有不同的反应。虽然许多提取物的生长抑制活性不受CDR1过表达的影响，但观察到对其中一些提取物的敏感性增加。相反，包括吐根花椒乙酸乙酯提取物在内的无明显抗念珠菌活性的提取物会被Cdr1p解毒。进一步的分级分离实验表明，该提取物中存在一种无毒的Cdr1p介导的酮康唑耐药调节剂以及具有生长抑制作用的Cdr1p底物。
