The peptidoglycan of stationary-phase Mycobacterium tuberculosis predominantly contains cross-links generated by L,D-transpeptidation
The peptidoglycan of stationary-phase Mycobacterium tuberculosis predominantly contains cross-links generated by L,D-transpeptidation
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DOI：
10.1128/jb.00239-08
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发表时间：
2008-06-01
影响因子：
3.2
通讯作者：
Mainardi, Jean-Luc
中科院分区：
文献类型：
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作者：
Lavollay, Marie;Arthur, Michel;Mainardi, Jean-Luc
我们对结核分枝杆菌持续处于“休眠”状态的机制的理解对于开发有效的组织灭菌疗法至关重要。模型系统中的基因表达谱揭示了一种复杂的适应性反应，被认为赋予了M。结核病患者有能力在联合抗生素治疗后存活数月。我们在这里表明，这种适应性反应可能涉及肽聚糖网络的重塑，由青霉素结合蛋白的D，D-转肽酶活性产生的4 -> 3个交联被L，D特异性转肽酶产生的3 -> 3个交联取代。先前显示在营养饥饿时上调的候选基因被发现编码在3 -> 3交联形成中有活性的L，D-转肽酶。这种酶Ldt（Mt 1）被碳青霉烯类灭活，碳青霉烯类是一类β-内酰胺类抗生素，不易被M.结核病β-内酰胺酶。Ldt（Mt 1）和碳青霉烯类可能是根除持久性M的靶点和药物家族。结核
Our understanding of the mechanisms used by Mycobacterium tuberculosis to persist in a "dormant" state is essential to the development of therapies effective in sterilizing tissues. Gene expression profiling in model systems has revealed a complex adaptive response thought to endow M. tuberculosis with the capacity to survive several months of combinatorial antibiotic treatment. We show here that this adaptive response may involve remodeling of the peptidoglycan network by substitution of 4 -> 3 cross-links generated by the D,D-transpeptidase activity of penicillin-binding proteins by 3 -> 3 cross-links generated by a transpeptidase of L,D specificity. A candidate gene, previously shown to be upregulated upon nutrient starvation, was found to encode an L,D-transpeptidase active in the formation of 3 -> 3 cross-links. The enzyme, Ldt(Mt1), was inactivated by carbapenems, a class of beta-lactam antibiotics that are poorly hydrolyzed by the M. tuberculosis beta-lactamases. Ldt(Mt1), and carbapenems may therefore represent a target and a drug family relevant to the eradication of persistent M. tuberculosis.