Nguyen Liem, Thompson Charles J
Department of Microbiology and Immunology, Life Sciences Centre, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Trends Microbiol. 2006 Jul;14(7):304-12. doi: 10.1016/j.tim.2006.05.005. Epub 2006 Jun 8.
The intrinsic resistance of Mycobacterium tuberculosis and related pathogens to most common antibiotics limits chemotherapeutic options to treat tuberculosis and other mycobacterial diseases. Resistance has traditionally been attributed to the unusual multi-layer cell envelope that functions as an effective barrier to the penetration of antibiotics. Recent insights into mechanisms that neutralize the toxicity of antibiotics in the cytoplasm have revealed systems that function in synergy with the permeability barrier to provide intrinsic resistance. Here, we highlight the growing pool of information about internal, antibiotic-responsive regulatory proteins and corresponding resistance genes, and present new concepts that rationalize how they might have evolved. Pharmaceutical inhibition of these intrinsic systems could make many previously available antibiotics active against M. tuberculosis.
结核分枝杆菌及相关病原体对大多数常见抗生素的固有耐药性限制了治疗结核病和其他分枝杆菌病的化疗选择。传统上，耐药性归因于异常的多层细胞包膜，它作为抗生素渗透的有效屏障。最近对中和细胞质中抗生素毒性机制的深入了解揭示了与通透性屏障协同作用以提供固有耐药性的系统。在这里，我们强调了关于内部抗生素反应性调节蛋白和相应耐药基因的信息不断增加，并提出了合理化它们可能如何进化的新概念。对这些固有系统的药物抑制可能会使许多以前可用的抗生素对结核分枝杆菌具有活性。
