Siddiqui Ruqaiyyah, Abjani Farhat, Yeo Chien Ing, Tiekink Edward R T, Khan Naveed Ahmed
Department of Biological Sciences, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor, Malaysia.
Research Centre for Crystalline Materials, Sunway University, 47500 Bandar Sunway, Selangor, Malaysia.
J Negat Results Biomed. 2017 Apr 3;16(1):6. doi: 10.1186/s12952-017-0070-7.
Gold compounds have shown promise in the treatment of non-communicable diseases such as rheumatoid arthritis and cancer, and are considered of value as anti-microbial agents against Gram-negative and Gram-positive bacteria, and have anti-parasitic properties against Schistosoma mansoni, Trypanosoma brucei, Plasmodium falciparum, Leishmania infantinum, Giardia lamblia, and Entamoeba histolytica. They are known to affect enzymatic activities that are required for the cellular respiration processes.
Anti-amoebic effects of phosphanegold(I) thiolates were tested against clinical isolate of A. castellanii belonging to the T4 genotype by employing viability assays, growth inhibition assays, encystation assays, excystation assays, and zymographic assays.
The treatment of A. castellanii with the phosphanegold(I) thiolates tested (i) had no effect on the viability of A. castellanii as determined by Trypan blue exclusion test, (ii) did not affect amoebae growth using PYG growth medium, (iii) did not inhibit cellular differentiation, and (iv) had no effect on the extracellular proteolytic activities of A. castellanii.
Being free-living amoeba, A. castellanii is a versatile respirator and possesses respiratory mechanisms that adapt to various aerobic and anaerobic environments to avoid toxic threats and adverse conditions. For the first time, our findings showed that A. castellanii exhibits resistance to the toxic effects of gold compounds and could prove to be an attractive model to study mechanisms of metal resistance in eukaryotic cells.
金化合物在类风湿关节炎和癌症等非传染性疾病的治疗中显示出前景，被认为是对抗革兰氏阴性菌和革兰氏阳性菌的有价值的抗菌剂，并且对曼氏血吸虫、布氏锥虫、恶性疟原虫、婴儿利什曼原虫、蓝氏贾第鞭毛虫和溶组织内阿米巴具有抗寄生虫特性。已知它们会影响细胞呼吸过程所需的酶活性。
通过活力测定、生长抑制测定、包囊化测定、脱囊化测定和酶谱测定，测试了膦金（I）硫醇盐对属于T4基因型的卡氏棘阿米巴临床分离株的抗阿米巴作用。
用测试的膦金（I）硫醇盐处理卡氏棘阿米巴，（i）通过台盼蓝排斥试验确定对卡氏棘阿米巴的活力没有影响，（ii）使用PYG生长培养基不影响阿米巴的生长，（iii）不抑制细胞分化，并且（iv）对卡氏棘阿米巴的细胞外蛋白水解活性没有影响。
作为自由生活的阿米巴，卡氏棘阿米巴是一种多功能的呼吸者，拥有适应各种有氧和无氧环境以避免有毒威胁和不利条件的呼吸机制。我们的研究结果首次表明，卡氏棘阿米巴对金化合物的毒性作用具有抗性，并且可能被证明是研究真核细胞中金属抗性机制的有吸引力的模型。
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