Gagneux Sebastien, Long Clara Davis, Small Peter M, Van Tran, Schoolnik Gary K, Bohannan Brendan J M
Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA.
Science. 2006 Jun 30;312(5782):1944-6. doi: 10.1126/science.1124410.
Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.
数学模型预测，耐多药结核病流行的未来将取决于耐药性的适合度代价。我们发现，在实验室衍生的结核分枝杆菌突变体中，利福平耐药性普遍与竞争性适合度代价相关，且这种代价由特定的耐药突变和菌株遗传背景决定。相比之下，我们证明，患者的长期治疗可导致无适合度缺陷的耐多药菌株，而且具有低适合度代价或无适合度代价耐药突变的菌株在临床分离株中也最为常见。
