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Gene Review

mexA  -  resistance-nodulation-cell division (RND)...

Pseudomonas aeruginosa PAO1

 
 
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Disease relevance of mexA

  • Assembly of the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa: identification and characterization of mutations in mexA compromising MexA multimerization and interaction with MexB [1].
 

High impact information on mexA

  • 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 [2].
  • Using fusions to gfp, we were able to analyze spatial and temporal expression of mexA and mexC in the developing biofilm [3].
  • RESULTS: While there was a significant correlation between expression of the quorum-sensing regulatory genes and production of pyocyanin and elastase, there was no correlation with expression of mexA or with antimicrobial resistance [4].
  • The purified protein was shown to bind ca. 200 bp upstream of mexA, at two sites, each of which contains a repeat of the nucleotide sequence GTTGA in inverse orientation [5].
  • To envisage the role of these proteins in antibiotic extrusion and resistance, we employed the gene replacement technique to construct mutants deficient in mexA, mexB, or oprM, and all possible combinations of these genes [6].
 

Biological context of mexA

  • 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 [7].
  • A reverse transcription PCR method was used to quantify mexA transcripts and showed an increased transcription rate of mexA in this strain, compared with a PAO1 control strain [8].
  • To elucidate the molecular mechanism by which the MexR repressor regulates expression of the MexAB-OprM efflux pump, we investigated MexR and the mexR-mexA intergenic DNA (mexOP) interaction, and transcription of the mexA-lacZ reporter gene containing different lengths of mexOP [9].
  • One strain contained a single mutation in mexR, a regulator of mexAB-oprM expression, that did not adversely affect the MexR amino acid sequence, and three isolates contained the same, single base change in the mexA-mexR intergenic region [10].
 

Other interactions of mexA

  • In nalB mutants, which overexpress OprM, we observed a four- to eightfold increase in the expression of mexA, mexB, and oprM genes [11].
  • Using a mexA-phoA fusion, expression of the efflux genes was assessed as a function of growth in a variety of strains [12].
  • Putative recognition sequences for AlgT/U and RpoN were identified upstream of mexA, but algT/U and rpoN null mutants also had no effect on mexAmexBoprM expression [12].

References

  1. Assembly of the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa: identification and characterization of mutations in mexA compromising MexA multimerization and interaction with MexB. Nehme, D., Li, X.Z., Elliot, R., Poole, K. J. Bacteriol. (2004) [Pubmed]
  2. 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]
  3. Multidrug efflux pumps: expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms. De Kievit, T.R., Parkins, M.D., Gillis, R.J., Srikumar, R., Ceri, H., Poole, K., Iglewski, B.H., Storey, D.G. Antimicrob. Agents Chemother. (2001) [Pubmed]
  4. Expression of the las and rhl quorum-sensing systems in clinical isolates of Pseudomonas aeruginosa does not correlate with efflux pump expression or antimicrobial resistance. Bratu, S., Gupta, J., Quale, J. J. Antimicrob. Chemother. (2006) [Pubmed]
  5. MexR repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa: identification of MexR binding sites in the mexA-mexR intergenic region. Evans, K., Adewoye, L., Poole, K. J. Bacteriol. (2001) [Pubmed]
  6. The role of mex-gene products in antibiotic extrusion in Pseudomonas aeruginosa. Yoneyama, H., Ocaktan, A., Tsuda, M., Nakae, T. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  7. 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]
  8. Detection of an IS21 insertion sequence in the mexR gene of Pseudomonas aeruginosa increasing beta-lactam resistance. Boutoille, D., Corvec, S., Caroff, N., Giraudeau, C., Espaze, E., Caillon, J., Plésiat, P., Reynaud, A. FEMS Microbiol. Lett. (2004) [Pubmed]
  9. Molecular mechanism of MexR-mediated regulation of MexAB-OprM efflux pump expression in Pseudomonas aeruginosa. Saito, K., Eda, S., Maseda, H., Nakae, T. FEMS Microbiol. Lett. (2001) [Pubmed]
  10. Contribution of multidrug efflux pumps to multiple antibiotic resistance in veterinary clinical isolates of Pseudomonas aeruginosa. Beinlich, K.L., Chuanchuen, R., Schweizer, H.P. FEMS Microbiol. Lett. (2001) [Pubmed]
  11. Analysis of antibiotic resistance gene expression in Pseudomonas aeruginosa by quantitative real-time-PCR. Dumas, J.L., van Delden, C., Perron, K., Köhler, T. FEMS Microbiol. Lett. (2006) [Pubmed]
  12. The MexA-MexB-OprM multidrug efflux system of Pseudomonas aeruginosa is growth-phase regulated. Evans, K., Poole, K. FEMS Microbiol. Lett. (1999) [Pubmed]
 
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