School of Civil and Environmental Engineering, Georgia Institute of Technology, 311 Ferst Dr, Atlanta, GA 30332-0512, USA.
Environ Microbiol. 2011 Apr;13(4):1010-7. doi: 10.1111/j.1462-2920.2010.02406.x. Epub 2011 Jan 18.
Antibiotic resistance in pathogens can be mediated by catabolic enzymes thought to originate from soil bacteria, but the physiological functions and evolutionary origins of the enzymes in natural ecosystems are poorly understood. 2-Nitroimidazole (2NI) is a natural antibiotic and an analogue of the synthetic nitroimidazoles used for treatment of tuberculosis, Chagas' disease and cancer. Mycobacterium sp. JS330 was isolated from soil based on its ability to use 2NI as a sole growth substrate. The initial step in the degradation pathway is the hydrolytic denitration of 2NI to produce imidazol-2-one and nitrite. The amino acid sequence of 2NI nitrohydrolase is highly divergent from those of biochemically characterized enzymes, and it confers drug resistance when it is heterologously expressed in Escherichia coli. The unusual enzymatic reaction seems likely to determine the flux of nitroimidazole in natural ecosystems and also represents the discovery of a previously unreported drug resistance mechanism in soil before its identification in clinical situations.
病原体中的抗生素耐药性可以通过代谢酶介导，这些酶被认为源自土壤细菌，但在自然生态系统中，这些酶的生理功能和进化起源还知之甚少。2-硝基咪唑（2NI）是一种天然抗生素，也是用于治疗肺结核、恰加斯病和癌症的合成硝基咪唑类药物的类似物。分枝杆菌 JS330 是根据其利用 2NI 作为唯一生长基质的能力从土壤中分离出来的。降解途径的第一步是 2NI 的水解脱氮，生成咪唑-2-酮和亚硝酸盐。2NI 硝水解酶的氨基酸序列与生物化学特征酶的序列差异很大，当它在大肠杆菌中异源表达时，会赋予其药物抗性。这种不寻常的酶促反应似乎很可能决定了硝基咪唑在自然生态系统中的通量，而且在其在临床情况下被发现之前，这代表了在土壤中发现的一种以前未报道的耐药机制。
