VanX, a bacterial D-alanyl-D-alanine dipeptidase: Resistance, immunity, or survival function?
VanX, a bacterial D-alanyl-D-alanine dipeptidase: Resistance, immunity, or survival function?
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DOI：
10.1073/pnas.96.20.11028
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发表时间：
1999-09-28
影响因子：
11.1
通讯作者：
Walsh, CT
中科院分区：
文献类型：
--
作者：
Lessard, IAD;Walsh, CT
在革兰氏阳性菌和革兰氏阴性菌中均检测到了含锌的 D-丙氨酰-D-丙氨酸 (D-Ala-D-Ala) 二肽酶 VanX，它似乎已经适应了至少三种不同的生理作用。在致病性万古霉素耐药肠球菌中，vanX 是五基因簇的一部分，该五基因簇被打开以重新编程细胞壁生物合成，以产生终止于 D-丙氨酰-D-乳酸 (D-Ala-D-乳酸) 而不是 D-Ala-D-Ala 的肽聚糖链前体。修饰后的肽聚糖对万古霉素的亲和力降低了 1,000 倍，这是观察到的表型耐药性的原因。在糖肽抗生素生产者 Toyocaensis 和 Amylocatopsis orientalis 中，vanHAX 操纵子可能与抗生素生物合成基因共同进化，通过将细胞壁末端重编程为 D-Ala-D-乳酸作为抗生素生物合成来提供免疫力。已启动。在革兰氏阴性细菌埃希氏菌中，由于糖肽类抗生素无法穿透外膜渗透性屏障，因此从未受到糖肽抗生素的挑战，在稳定期，vanX 同源物 (ddpX) 与假定的二肽转运系统 (ddpABCDF) 通过转录因子 RpoS (sigma(s)) 共转录。当细胞壁交联重塑时，DdpX 和通透酶的联合作用将允许 D-Ala-D-Ala 水解，从周质转运回细胞质，然后 D-Ala 产物可以被氧化，作为细胞在饥饿条件下生存的能源。
The zinc containing D-alanyl-D-alanine (D-Ala-D-Ala) dipeptidase VanX has been detected in both Grampositive and Gram-negative bacteria, where it appears to have adapted to at least three distinct physiological roles. In pathogenic vancomycin-resistant enterococci, vanX is part of a five-gene cluster that is switched on to reprogram cell-wall biosynthesis to produce peptidoglycan chain precursors terminating in D-alanyl-D-lactate (D-Ala-D-lactate) rather than D-Ala-D-Ala. The modified peptidoglycan exhibits a 1,000-fold decrease in affinity for vancomycin, accounting for the observed phenotypic resistance, In the glycopeptide antibiotic producers Streptomyces toyocaensis and Amylocatopsis orientalis, a vanHAX operon may have coevolved with antibiotic biosynthesis genes to provide immunity by reprogramming cell-wall termini to D-Ala-D-lactate as antibiotic biosynthesis is initiated. In the Gram-negative bacterium Escherichia call, which is never challenged by the glycopeptide antibiotics because they cannot penetrate the outer membrane permeability barrier, the vanX homologue (ddpX) is cotranscribed with a putative dipeptide transport system (ddpABCDF) in stationary phase by the transcription factor RpoS (sigma(s)). The combined action of DdpX and the permease would permit hydrolysis of D-Ala-D-Ala transported back into the cytoplasm from the periplasm as cell-wall crosslinks are refashioned, The D-Ala product could then be oxidized as an energy source for cell survival under starvation conditions.