Paritala Hanumantharao, Carroll Kate S
Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA.
Infect Disord Drug Targets. 2013 Apr;13(2):85-115. doi: 10.2174/18715265113139990022.
The identification of new antibacterial targets is urgently needed to address multidrug resistant and latent tuberculosis infection. Sulfur metabolic pathways are essential for survival and the expression of virulence in many pathogenic bacteria, including Mycobacterium tuberculosis. In addition, microbial sulfur metabolic pathways are largely absent in humans and therefore, represent unique targets for therapeutic intervention. In this review, we summarize our current understanding of the enzymes associated with the production of sulfated and reduced sulfur-containing metabolites in Mycobacteria. Small molecule inhibitors of these catalysts represent valuable chemical tools that can be used to investigate the role of sulfur metabolism throughout the Mycobacterial lifecycle and may also represent new leads for drug development. In this light, we also summarize recent progress made in the development of inhibitors of sulfur metabolism enzymes.
迫切需要鉴定新的抗菌靶点，以应对多重耐药和潜伏性结核感染。硫代谢途径对于包括结核分枝杆菌在内的许多致病细菌的生存和毒力表达至关重要。此外，人类基本不存在微生物硫代谢途径，因此，它是治疗干预的独特靶点。在这篇综述中，我们总结了目前对分枝杆菌中与硫酸化和还原态含硫代谢物产生相关酶的理解。这些催化剂的小分子抑制剂是有价值的化学工具，可用于研究硫代谢在分枝杆菌整个生命周期中的作用，也可能代表药物开发的新线索。鉴于此，我们还总结了硫代谢酶抑制剂开发方面的最新进展。
