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Gene Review

mexR  -  multidrug resistance operon repressor MexR

Pseudomonas aeruginosa PAO1

 
 
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Disease relevance of mexR

  • Mutations in genes mexR and nalC have previously been shown to drive overexpression of the MexAB-OprM multidrug efflux system in Pseudomonas aeruginosa [1].
  • The remaining isolates from keratitis, endophthalmitis, contact lens associated red eye (CLARE), and contact lens storage cases showed MIC values below 1 mg/l. Several allelic forms of gyrA and a single variation in the mexR gene product were detected in 10 ciprofloxacin susceptible strains [2].
 

High impact information on mexR

  • Four of them were nalB mutants with alterations in the repressor gene mexR, three of them appeared to be nalC mutants deficient in gene PA3721 and overexpressing gene PA3720, and one strain was a nalB nalC double mutant [3].
  • Of the four isolates exhibiting wild-type MexAB-OprM expression despite the MexR alteration, two appeared to harbor secondary mutations in the mexA-mexR intergenic region and one harbored secondary mutations in the putative ribosome binding site located upstream of the mexAB oprM operon [4].
  • To determine whether mutations in mexR, the regulator gene of the mexA-mexB-oprM efflux operon, could account for the overproduction of the efflux system, sequencing experiments were carried out with the 11 bacterial pairs [5].
  • Two resistant strains had point mutations in mexR that yielded single amino acid changes in the protein MexR, while another strain did not show any mutation in mexR or in the promoter region upstream of mexR [5].
  • A mexR knockout mutant showed a twofold increase in expression of both plasmid-borne and chromosomal mexA-reporter gene fusions compared with the MexR+ parent strain, indicating that the mexR gene product negatively regulates expression of the mexA-mexB-oprM operon [6].
 

Biological context of mexR

  • Consistent with the increased expression of the efflux operon in the mexR mutant, the mutant showed an increase (relative to its MexR+ parent) in resistance to several antimicrobial agents [6].
  • The region upstream of the multiple antibiotic resistance efflux operon mexA-mexB-oprM in Pseudomonas aeruginosa was sequenced, and a gene, mexR, was identified [6].
  • The nucleotide sequences of the mexR genes of OCR1 and its parental strain revealed a single base substitution in the former which would cause a predicted substitution of Trp for Arg at position 69 of its mexR product [6].
  • Introduction of a mexR knockout mutation in strain OCR1 eliminated this increase in efflux gene expression and, as expected, increased the susceptibility of the strain to a variety of antibiotics [6].
  • Mutations in mexR yield a multidrug resistance phenotype in nalB mutants of Pseudomonas aeruginosa as a result of derepression of the mexAB-oprM multidrug efflux operon [7].
 

Associations of mexR with chemical compounds

 

Other interactions of mexR

  • Finally, three isolates, named agrW mutants, overproduced MexXY and had an intact mexZ gene, and four strains overproduced MexAB-OprM and had intact mexR and PA3721 genes (nalD mutants) [3].
  • Four strains had mexR and two strains nfxB mutations [10].
 

Analytical, diagnostic and therapeutic context of mexR

References

  1. Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug resistance in laboratory and clinical isolates of Pseudomonas aeruginosa. Sobel, M.L., Hocquet, D., Cao, L., Plesiat, P., Poole, K. Antimicrob. Agents Chemother. (2005) [Pubmed]
  2. Ciprofloxacin susceptibility of Pseudomonas aeruginosa isolates from keratitis. Lomholt, J.A., Kilian, M. The British journal of ophthalmology. (2003) [Pubmed]
  3. Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Llanes, C., Hocquet, D., Vogne, C., Benali-Baitich, D., Neuwirth, C., Plésiat, P. Antimicrob. Agents Chemother. (2004) [Pubmed]
  4. Genetic and phenotypic variations of a resistant Pseudomonas aeruginosa epidemic clone. Hocquet, D., Bertrand, X., Köhler, T., Talon, D., Plésiat, P. Antimicrob. Agents Chemother. (2003) [Pubmed]
  5. In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa overexpressing the active efflux system MexA-MexB-OprM. Ziha-Zarifi, I., Llanes, C., Köhler, T., Pechere, J.C., Plesiat, P. Antimicrob. Agents Chemother. (1999) [Pubmed]
  6. Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression. Poole, K., Tetro, K., Zhao, Q., Neshat, S., Heinrichs, D.E., Bianco, N. Antimicrob. Agents Chemother. (1996) [Pubmed]
  7. The mexR repressor of the mexAB-oprM multidrug efflux operon in Pseudomonas aeruginosa: characterization of mutations compromising activity. Adewoye, L., Sutherland, A., Srikumar, R., Poole, K. J. Bacteriol. (2002) [Pubmed]
  8. Carbapenem resistance mechanisms in Pseudomonas aeruginosa: alterations of porin OprD and efflux proteins do not fully explain resistance patterns observed in clinical isolates. El Amin, N., Giske, C.G., Jalal, S., Keijser, B., Kronvall, G., Wretlind, B. APMIS (2005) [Pubmed]
  9. Mutation in mexR-gene leading to drug resistance in corneal keratitis in human. Suman, G., Khan, M., Sabitha, K., Jamil, K. Indian J. Exp. Biol. (2006) [Pubmed]
  10. Mechanisms of quinolone resistance in clinical strains of Pseudomonas aeruginosa. Jalal, S., Wretlind, B. Microb. Drug Resist. (1998) [Pubmed]
  11. Organic solvent-tolerant mutants of Pseudomonas aeruginosa display multiple antibiotic resistance. Li, X.Z., Poole, K. Can. J. Microbiol. (1999) [Pubmed]
 
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