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MarR is a regulator of multiple antibiotic resistance in Escherichia coli. It is the prototypical member of the MarR family of regulatory proteins found in bacteria and archaea that play important roles in the development of antibiotic resistance, a global health problem. Here we describe the crystal structure of the MarR protein, determined at a resolution(More)
Treatment of infections is compromised worldwide by the emergence of bacteria that are resistant to multiple antibiotics. Although classically attributed to chromosomal mutations, resistance is most commonly associated with extrachromosomal elements acquired from other bacteria in the environment. These include different types of mobile DNA segments, such(More)
MarR negatively regulates expression of the multiple antibiotic resistance operon (marRAB) in Escherichia coli. In this study, it was demonstrated that sodium salicylate, plumbagin, 2, 4-dinitrophenol, and menadione-inducers of the marRAB operon in whole cells-all interfered with the repressor activity of MarR in vitro. It is proposed that these compounds(More)
MarR negatively regulates expression of the multiple antibiotic resistance (mar) locus in Escherichia coli. Superrepressor mutants, generated in order to study regions of MarR required for function, exhibited altered inducer recognition properties in whole cells and increased DNA binding to marO in vitro. Mutations occurred in three areas of the relatively(More)
Multidrug resistance in bacteria is generally attributed to the acquisition of multiple transposons and plasmids bearing genetic determinants for different mechanisms of resistance (48, 62). However, descriptions of intrinsic mechanisms that confer multidrug resistance have begun to emerge. The first of these was a chromosomally encoded multiple antibiotic(More)
The chromosomal multiple antibiotic resistance (mar) locus of Escherichia coli and other members of the Enterobacteriaceae controls resistance to multiple, structurally unrelated compounds including antibiotics, household disinfectants, organic solvents and other toxic chemicals. The Mar phenotype is induced following exposure to a variety of chemicals with(More)
MarR, the negative regulator of the Escherichia coli multiple antibiotic resistance (marRAB) operon, is a member of a newly recognized family of regulatory proteins. The amino acid sequences of these proteins do not display any apparent homologies to the DNA binding domains of prokaryotic transcription regulators and a DNA binding motif for any one of the(More)
A battle to control and curtail bacterial infectious diseases is being waged in our hospitals and communities through antibiotic therapies and vaccines targeting specific species. But what effects do these interventions have on the epidemiology of infections caused by the organisms that are part of our natural microbial flora? Gram-positive and(More)
Structure-based drug design was utilized to identify potent small-molecule inhibitors of proteins within the AraC family of bacterial transcription factors, which control virulence in medically important microbes. These agents represent a novel approach to fight infectious disease and may be less likely to promote resistance development. These compounds(More)
Expression of the Escherichia coli multiple antibiotic resistance marA gene cloned in Mycobacterium smegmatis produced increased resistance to multiple antimicrobial agents, including rifampin, isoniazid, ethambutol, tetracycline, and chloramphenicol. Cloned marR or marA cloned in the antisense direction had no effect. Resistance changes were lost with(More)