Bacillithiol and its unique drug resistance pathways in Bacilli

低分子量硫醇分子在抗生素耐药中起着重要作用。细胞内有许多酶，它们促进这些硫醇分子与抗生素的反应以及随后的解毒和从细胞中清除。为此，人类（和其他哺乳动物）使用一种叫做谷胱甘肽的硫醇分子，它是由氨基酸构成的。然而，并不是所有的生物体都能产生和利用谷胱甘肽。最近，我们在许多微生物病原体中发现了一类新的碳水化合物样生物硫醇，称为芽孢杆菌硫醇。这些细菌包括炭疽、食物中毒、尿路感染和耐甲氧西林金黄色葡萄球菌。该项目的目的是确定和表征这些细菌利用菌硫醇解毒各种抗生素的方式。了解谷胱甘肽和芽孢杆菌硫醇及其各自酶之间的差异可以为设计新药提供令人兴奋的机会，这些新药将选择性地针对耐药细菌的抗生素解毒机制，而不影响人体中发现的谷胱甘肽加工酶。

Low molecular weight thiol molecules play an important role in antibiotic drug resistance. There are many enzymes inside cells which facilitate the reaction of these thiol molecules with antibiotics and their subsequent detoxification and removal from the cell. For this purpose, humans (and other mammals) use a thiol molecule called glutathione, which is made from amino acids building blocks. However, not all organisms are able to produce and utilise glutathione. Recently, we have discovered a novel class of carbohydrate-like biothiol, called Bacillithiol, amongst a number of microbial pathogens. These include bacteria associated with anthrax, food poisoning, urinary tract infections and MRSA. The aim of this project is to identify and characterise the ways in which these bacteria utilise bacillithiol to detoxify various antibiotics. Understanding the differences between glutathione and bacillithiol and their respective enzymes could provide exciting opportunities to design new drugs that will selectively target antibiotic detoxification mechanisms in drug resistant bacteria without affecting the glutathione processing enzymes found in humans.