Homeostasis of glutathione is associated with polyamine-mediated β-lactam susceptibility in Acinetobacter baumannii ATCC 19606.
Homeostasis of glutathione is associated with polyamine-mediated β-lactam susceptibility in Acinetobacter baumannii ATCC 19606.
复制标题
谷胱甘肽的稳态与鲍曼不动杆菌 ATCC 19606 中多胺介导的 β-内酰胺敏感性相关。
DOI：
10.1128/aac.00692-13
复制
发表时间：
2013
影响因子：
4.9
通讯作者：
Seecoomar,Gomattie
中科院分区：
文献类型：
--
作者：
Kwon,DongH;Hekmaty,Saboor;Seecoomar,Gomattie
谷胱甘肽是一种三肽（l-γ-谷氨酰- l-半胱氨酸-甘氨酸）硫醇化合物，存在于许多细菌中，并维持适当的细胞氧化还原状态，从而保护细胞免受活性氧等有毒物质的侵害。多胺（精胺和亚精胺）是一种低分子量的脂肪聚阳离子，普遍存在于所有活细胞中，并调节许多细胞功能。我们之前报道过外源性多胺显著增强β-内酰胺相关多药耐药鲍曼不动杆菌对β-内酰胺的敏感性。本研究通过转座子诱变鲍曼不动杆菌ATCC 19606，鉴定了3个与多胺对β-内酰胺敏感性的差异相关基因。这三个基因都编码膜运输系统的组成部分。在鲍曼不动杆菌ATCC 19606中，一个编码谷胱甘肽转运atp结合蛋白的基因失活增加了细胞内谷胱甘肽的积累（~ 150 ~ ~ 200%），并显著降低了多胺对β-内酰胺敏感性的影响。用多胺培养细胞时，鲍曼不动杆菌ATCC 19606细胞内谷胱甘肽水平从~ 0.5 nmol显著降低到~ 0.2 nmol，而细胞外谷胱甘肽水平相应升高。然而，当细胞在有或没有多胺的情况下生长时，总谷胱甘肽（细胞内和细胞外）的水平不变。总之，这些结果表明外源性多胺诱导谷胱甘肽输出，导致细胞内谷胱甘肽水平下降，这可能产生不适当的细胞氧化还原状态，这与多胺介导的鲍曼不动杆菌β-内酰胺敏感性有关。这一发现可能为开发新的抗微生物药物和/或治疗多重耐药鲍曼不动杆菌的新策略提供线索。
Glutathione is a tripeptide (l-γ-glutamyl–l-cysteinyl–glycine) thiol compound existing in many bacteria and maintains a proper cellular redox state, thus protecting cells against toxic substances such as reactive oxygen species. Polyamines (spermine and spermidine) are low-molecular-weight aliphatic polycations ubiquitously presenting in all living cells and modulate many cellular functions. We previously reported that exogenous polyamines significantly enhanced β-lactam susceptibility of β-lactam-associated multidrug-resistant Acinetobacter baumannii. In this study, three genes differentially associated with the polyamine effects on β-lactam susceptibility were identified by transposon mutagenesis of A. baumannii ATCC 19606. All three genes encoded components of membrane transport systems. Inactivation of one of the genes encoding a putative glutathione transport ATP-binding protein increased the accumulation of intracellular glutathione (∼150 to ∼200%) and significantly decreased the polyamine effects on β-lactam susceptibility in A. baumannii ATCC 19606. When the cells were grown with polyamines, the levels of intracellular glutathione in A. baumannii ATCC 19606 significantly decreased from ∼0.5 to ∼0.2 nmol, while the levels of extracellular glutathione were correspondingly increased. However, the levels of total glutathione (intra- plus extracellular) were unchanged when the cells were grown with or without polyamines. Overall, these results suggest that exogenous polyamines induce glutathione export, resulting in decreased levels of intracellular glutathione, which may produce an improper cellular redox state that is associated with the polyamine-mediated β-lactam susceptibility of A. baumannii. This finding may provide a clue for development of new antimicrobial agents and/or novel strategies to treat multidrug-resistant A. baumannii.