Disease relevance of marA

• Overexpression of the marA or soxS regulatory gene in clinical topoisomerase mutants of Escherichia coli [1].
• Escherichia coli and Salmonella enterica serovar Typhimurium have evolved genetic systems, such as the soxR/S and marA regulons, to detoxify reactive oxygen species, like superoxide, which are formed as by-products of metabolism [2].
• Clinical Escherichia coli isolates, and isogenic strains lacking marA, soxS and rob, were studied in a murine model of ascending pyelonephritis, which is a clinically relevant model of urinary tract infection [3].
• We investigated the regulation of the MexEF-OprN multidrug efflux system of Pseudomonas aeruginosa, which is overexpressed in nfxC-type mutants and confers resistance to quinolones, chloramphenicol and trimethoprim [4].

High impact information on marA

• Genetics and regulation of outer membrane protein expression by quinolone resistance loci nfxB, nfxC, and cfxB [5].
• Overproduction of MppA repressed marA transcription in TP985 but not in other mppA or marR mutants [6].
• Complementation studies with a plasmid that constitutively expressed marA confirmed the involvement of mar in Salmonella with low-level antibiotic resistance and cyclohexane resistance, although the involvement of mar in down regulation of OmpF was unclear [7].
• Salicylate induced marA, whereas a number of antibiotics, disinfectants, and various growth conditions did not [7].
• We observed that the marA gene on high-copy-number plasmids increased the organic solvent tolerance of E. coli strains [8].

Chemical compound and disease context of marA

• Four of five clinical E. coli strains which overexpressed marA or soxS also showed enhanced triclosan resistance [9].

Biological context of marA

• Constitutive expression of marA conferred antibiotic resistance even in cells carrying a deletion of the chromosomal mar locus [10].
• A Tn5 insertion in marA inactivated the multiresistance phenotype of Mar mutants [11].
• Here, we investigate whether regulatory genes other than soxR/S and marA are active in response to oxidative stress in Salmonella and may function as virulence determinants [2].
• Mutations at this locus can activate the marRAB operon, in which marR encodes a putative repressor of mar transcription and marA encodes a putative transcriptional activator of defense genes against antibiotics and oxidants [12].
• Organisms lacking all three transcription factors (triple knockouts) were significantly less virulent than parental strains, and complementation studies demonstrated that the addition of marA, soxS and rob individually restored wild-type virulence in the triple-knockout strain [3].

Associations of marA with chemical compounds

• We report here that overexpression of the multidrug efflux pump locus acrAB, or of marA or soxS, both encoding positive regulators of acrAB, decreased susceptibility to triclosan 2-fold [9].
• We report here that certain mutations at a separate locus that we have named soxQ (at min 34) confer some of the phenotypes seen in soxR-constitutive strains, including resistance to menadione [13].

Analytical, diagnostic and therapeutic context of marA

• All isolates possessed fragments of marA with the predicted size of 408 bp when amplified using marA-specific primers by PCR [14].

References