The periplasmic murein peptide-binding protein MppA is a negative regulator of multiple antibiotic resistance in Escherichia coli.
MppA is a periplasmic binding protein in Escherichia coli essential for uptake of the cell wall murein tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate. We have found serendipitously that E. coli K-12 strains carrying a null mutation in mppA exhibit increased resistance to a wide spectrum of antibiotics and to cyclohexane. Normal sensitivity of the mppA mutant to these agents is restored by mppA expressed from a plasmid. As is observed in the multiple antibiotic resistance phenotype in E. coli cells, the mppA null 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 the mppA mutant. These and other data reported herein indicate that MppA functions upstream of MarA in a signal transduction pathway to negatively regulate the expression of marA and 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 the mppA null mutant indicate that MppA regulates a number of genes in addition to those already known to be controlled by MarA.
Li
H
H
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Park
J T
JT
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000378:metabolism; D001426:Bacterial Proteins; D001692:Biological Transport / Q000502:physiology; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D005968:Glutamate Decarboxylase / Q000235:genetics; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon / Q000502:physiology; D010457:Peptidoglycan / Q000378:metabolism; D033902:Periplasmic Binding Proteins; D010641:Phenotype; D017386:Sequence Homology, Amino Acid
D018528:ATP-Binding Cassette Transporters; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; C110966:MppA protein, E coli; C115788:Opp-1 protein, Staphylococcus aureus; D010457:Peptidoglycan; D033902:Periplasmic Binding Proteins; D005968:Glutamate Decarboxylase