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Biomedical subjects

M N Alekshun

Publications and source records attributed to M N Alekshun.

9 recordsLinked to original sources
PubMed2006

Commensals upon us.

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 gram-negative bacteria appear as new disease agents from among commensal flora. These include vancomycin resistant enterococci (VRE), community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), non-vaccine invasive serotypes of Streptococcus pneumoniae, new strains of non-type b Haemophilus influenzae and multi-drug resistant Escherichia coli. These examples illustrate how clinical improvements and widespread use and misuse of antibiotics have pushed evolution, allowing normally non-pathogenic strains to become infectious disease threats to human health.

Anti-Bacterial Agents↗
PubMed2001

The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution.

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 of 2.3 A. This is the first reported crystal structure of a member of this newly-described protein family. The structure shows MarR as a dimer with each subunit containing a winged-helix DNA binding motif.

Amino Acid Motifs↗
PubMed2000

Mutational analysis of MarR, the negative regulator of marRAB expression in Escherichia coli, suggests the presence of two regions required for DNA binding.

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 MarR homologues is currently unknown. In order to define regions of MarR required for DNA binding, mutant repressors, selected based on their ability to interfere with (negatively complement) the activity of wild-type MarR, were isolated. As determined using gel mobility shift assays, 13 out of 14 negative complementing mutants tested were unable to bind DNA in vitro. Three negative complementing alleles presumably specify truncated repressors and one of these proteins, a 120 residue MarR, can bind DNA in vitro. Most of the negative complementing mutations were clustered within two areas of MarR with features related to a helix-turn-helix DNA binding motif. These regions are presumed to be required for the DNA binding activity of the repressor.

Amino Acid Motifs↗
PubMed1999

The mar regulon: multiple resistance to antibiotics and other toxic chemicals.

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 aromatic rings.

Anti-Bacterial Agents↗
PubMed1999

Characterization of MarR superrepressor mutants.

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 small MarR protein (144 amino acids). It is surmised that superrepression results from increased DNA binding activities of these mutant proteins.

Bacterial Proteins↗
PubMed1999

Alteration of the repressor activity of MarR, the negative regulator of the Escherichia coli marRAB locus, by multiple chemicals in vitro.

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 can interact directly with MarR to affect its repressor activity.

2,4-Dinitrophenol↗
PubMed1998

Multidrug resistance following expression of the Escherichia coli marA gene in Mycobacterium smegmatis.

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 spontaneous loss of the plasmid bearing marA. A MarA mutant protein, having an insertional mutation within either of its two alpha-helices of the first putative helix-turn-helix domain, failed to produce the multiresistance phenotype in E. coli and M. smegmatis, indicating that this region is critical for MarA function. These results strongly suggest that E. coli marA functions in M. smegmatis and that a mar-like regulatory system exists in this organism.

Bacterial Proteins↗