The periplasmic murein peptide-binding protein MppA is a negative regulator of multiple antibiotic resistance in Escherichia coli.
The periplasmic murein peptide-binding protein MppA is a negative regulator of multiple antibiotic resistance in Escherichia coli.
复制标题
周质壁蛋白肽结合蛋白 MppA 是大肠杆菌多重抗生素耐药性的负调节因子。
DOI：
10.1128/jb.181.16.4842-4847.1999
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发表时间：
1999
影响因子：
3.2
通讯作者：
Park,JT
中科院分区：
文献类型：
--
作者：
Li,H;Park,JT
MppA是大肠杆菌中的一种周质结合蛋白，对摄取细胞壁胞壁蛋白三肽-丙氨酰-γ-d-谷氨酰-meso-二氨基庚二酸是必需的。我们偶然发现，E。携带mppA无效突变的大肠杆菌K-12菌株对广谱抗生素和环己烷的耐药性增加。从质粒中表达的mppA恢复了ppA突变体对这些药物的正常敏感性。如在E.在大肠杆菌中，themppAnull突变体过量产生转录激活因子MarA，导致作为药物外排泵的膜结合AcrAB蛋白的表达。类似于在多重抗生素抗性表型中观察到的OmpF产生减少也见于themppA突变体。本文报道的这些和其他数据表明，MppA在信号转导途径中在MarA的上游起作用，以负调控MarA的表达，从而负调控MarA驱动的多重抗生素抗性。过量生产的细胞质GadA和GadB和几个身份不明的细胞质膜蛋白，以及减少的外膜蛋白，Ompp，在themppAnull突变体的量表明，MppA调节一些基因，除了那些已经知道由MarA控制。
MppA is a periplasmic binding protein inEscherichia coliessential for uptake of the cell wall murein tripeptidel-alanyl-γ-d-glutamyl-meso-diaminopimelate. We have found serendipitously thatE. coliK-12 strains carrying a null mutation inmppAexhibit increased resistance to a wide spectrum of antibiotics and to cyclohexane. Normal sensitivity of themppAmutant to these agents is restored bymppAexpressed from a plasmid. As is observed in the multiple antibiotic resistance phenotype inE. colicells, themppAnull mutant overproduces the transcriptional activator, MarA, resulting in expression of the membrane-bound AcrAB proteins that function as a drug efflux pump. Reduced production of OmpF similar to that observed in the multiple antibiotic resistance phenotype is also seen in themppAmutant. These and other data reported herein indicate that MppA functions upstream of MarA in a signal transduction pathway to negatively regulate the expression ofmarAand hence of the MarA-driven multiple antibiotic resistance. Overproduction of cytoplasmic GadA and GadB and of several unidentified cytoplasmic membrane proteins as well as reduction in the amount of the outer membrane protein, OmpP, in themppAnull mutant indicate that MppA regulates a number of genes in addition to those already known to be controlled by MarA.