Hoffman Amanda E, Miles Leann, Greenfield Tiffany J, Shoen Carolyn, DeStefano Michelle, Cynamon Michael, Doyle Robert P
Department of Chemistry, Syracuse University, Syracuse, NY, 13244, USA.
Biometals. 2015 Apr;28(2):415-23. doi: 10.1007/s10534-015-9825-0. Epub 2015 Feb 7.
The minimal inhibitory concentrations (MICs) of copper and cobalt based dimeric pyrophosphate complexes with capping 1,10-phenanthroline groups on clinical isolates of C. albicans (28 isolates), C. krusei (20 isolates) and C. tropicalis (20 isolates) are reported. C. albicans was inhibited by the cobalt complex better than by the copper complex, while C. krusei demonstrated the opposite results. C. tropicalis showed similar sensitivities to both metals in terms of calculated MIC50 values but was more sensitive to cobalt when MIC90 values were noted. Knockout strains of C. albicans that had the copper efflux protein P-type ATPase (CRP1), the copper binding metallothionein CUP1 or both CRP1/CUP1 removed clearly demonstrate that the origins of copper resistant in C. albicans lies primarily in the P-type ATPase, with the MT playing an important secondary role in the absence of the efflux protein. This study suggests that certain strains of Candida have evolved to protect against particular metal ions and that in the case of C. albicans, a primary invasive fungal species, cobalt may be a good starting-point for new therapeutic development.
报道了带有封端1,10-菲咯啉基团的铜和钴基二聚焦磷酸盐配合物对白色念珠菌(28株分离株)、克鲁斯念珠菌(20株分离株)和热带念珠菌(20株分离株)临床分离株的最低抑菌浓度(MICs)。白色念珠菌对钴配合物的敏感性高于铜配合物,而克鲁斯念珠菌则呈现相反结果。就计算出的MIC50值而言,热带念珠菌对两种金属表现出相似的敏感性,但在记录MIC90值时对钴更敏感。敲除了铜转运蛋白P型ATP酶(CRP1)、铜结合金属硫蛋白CUP1或两者CRP1/CUP1的白色念珠菌敲除菌株清楚地表明,白色念珠菌对铜耐药的根源主要在于P型ATP酶,在没有外排蛋白的情况下,金属硫蛋白起重要的次要作用。这项研究表明,某些念珠菌菌株已经进化出抵御特定金属离子的能力,对于主要的侵袭性真菌物种白色念珠菌而言,钴可能是新治疗方法开发的一个良好起点。