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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

mefE  -  macolide ABC transporter permease

Streptococcus pneumoniae R6

 
 
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Disease relevance of mefE

  • After increasing from 1995 to 1999, invasive erythromycin-nonsusceptible Streptococcus pneumoniae rates per 100,000 decreased 53.6% in children from Baltimore, Maryland (US), from 1999 to 2001, which was partially attributed to strains related to the mefE-carrying England14-9 clone [1].
  • Distribution of subclasses mefA and mefE of the mefA gene among clinical isolates of macrolide-resistant (M-phenotype) Streptococcus pneumoniae, viridans group streptococci, and Streptococcus pyogenes [2].
  • Increase of macrolide-resistant Streptococcus pneumoniae-expressing mefE or ermB gene in the nasopharynx among children with otitis media [3].
 

High impact information on mefE

  • In the United States, most erythromycin-resistant pneumococci exhibit the newly described M phenotype (resistance to erythromycin alone), associated with the mefE gene [4].
  • The expression of both mefE and mel was inducible by erythromycin [5].
  • Two macrolide-susceptible (PCR negative for both mefE and ermB) and 11 efflux-producing macrolide-resistant [PCR-positive for mefE and negative for ermB) S. pneumoniae strains with various telithromycin MICs (0.015 to 1 microg/ml) were tested [6].
  • The first 2 open-reading frames (ORFs) of the element formed an operon composed of mefE and a predicted adenosine triphosphate-binding cassette homologous to msrA [7].
  • In a rat lung model of infection, ABT-773 demonstrated 50% effective doses lower than those of comparator macrolides when evaluated against the following strains of S. pneumoniae: a macrolide-lincosamide-streptogramin B-susceptible strain, an ermB strain, and an mefE strain [8].
 

Chemical compound and disease context of mefE

 

Biological context of mefE

  • The DNA sequences of mefE were nearly identical, with only 2-nucleotide differences between genes from any two strains [9].
  • The mefE gene was found on the 5' end of a 5.5- or 5.4-kb insertion designated as the macrolide efflux genetic assembly (mega), which is found in > or =4 distinct sites of the pneumococcal genome [7].
  • Additionally, ABT-773 improved the survival of mice infected with resistant S. pneumoniae containing either the ermB gene, the mefE gene, or altered penicillin binding protein genes [8].
  • Strains of S. pneumoniae were constructed to confirm that mefE is necessary to confer erythromycin resistance and to explore the substrate specificity of the pump; no substrates other than 14- and 15-membered macrolides were identified [9].
 

Associations of mefE with chemical compounds

  • Clindamycin was active only against macrolide-resistant strains containing mefE (MIC(50), 0.06 microgram/ml; MIC(90), 0.125 microgram/ml) [10].
  • Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s were 0.016 to 0.03 and 0.125 microgram/ml, respectively [10].
  • With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin contained ermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients [11].
  • Macrolide-resistant isolates were studied for the presence of ermAM (a ribosomal methylase gene), mefE (a macrolide efflux gene), and tetM (the class M tetracycline resistance gene) [12].
  • The ability of 50 sequential subcultures in subinhibitory concentrations of telithromycin (HMR 3647), azithromycin, clarithromycin, erythromycin A, roxithromycin, clindamycin, and pristinamycin to select for resistance was studied in five macrolide-susceptible and six macrolide-resistant pneumococci containing mefE or ermB [13].
 

Analytical, diagnostic and therapeutic context of mefE

References

  1. Erythromycin-nonsusceptible Streptococcus pneumoniae in children, 1999-2001. McEllistrem, M.C., Adams, J.M., Shutt, K., Sanza, L.T., Facklam, R.R., Whitney, C.G., Jorgensen, J.H., Harrison, L.H. Emerging Infect. Dis. (2005) [Pubmed]
  2. Distribution of subclasses mefA and mefE of the mefA gene among clinical isolates of macrolide-resistant (M-phenotype) Streptococcus pneumoniae, viridans group streptococci, and Streptococcus pyogenes. Ardanuy, C., Tubau, F., Liñares, J., Domínguez, M.A., Pallarés, R., Martín, R. Antimicrob. Agents Chemother. (2005) [Pubmed]
  3. Increase of macrolide-resistant Streptococcus pneumoniae-expressing mefE or ermB gene in the nasopharynx among children with otitis media. Hotomi, M., Billal, D.S., Shimada, J., Suzumoto, M., Yamauchi, K., Fujihara, K., Yamanaka, N. Laryngoscope (2005) [Pubmed]
  4. Emergence of the M phenotype of erythromycin-resistant pneumococci in South Africa. Widdowson, C.A., Klugman, K.P. Emerging Infect. Dis. (1998) [Pubmed]
  5. Macrolide efflux in Streptococcus pneumoniae is mediated by a dual efflux pump (mel and mef) and is erythromycin inducible. Ambrose, K.D., Nisbet, R., Stephens, D.S. Antimicrob. Agents Chemother. (2005) [Pubmed]
  6. Pharmacodynamic activity of telithromycin at simulated clinically achievable free-drug concentrations in serum and epithelial lining fluid against efflux (mefE)-producing macrolide-resistant Streptococcus pneumoniae for which telithromycin MICs vary. Zhanel, G.G., Johanson, C., Laing, N., Hisanaga, T., Wierzbowski, A., Hoban, D.J. Antimicrob. Agents Chemother. (2005) [Pubmed]
  7. Structure and dissemination of a chromosomal insertion element encoding macrolide efflux in Streptococcus pneumoniae. Gay, K., Stephens, D.S. J. Infect. Dis. (2001) [Pubmed]
  8. Efficacies of ABT-773, a new ketolide, against experimental bacterial infections. Mitten, M.J., Meulbroek, J., Nukkala, M., Paige, L., Jarvis, K., Oleksijew, A., Tovcimak, A., Hernandez, L., Alder, J.D., Ewing, P., Or, Y.S., Ma, Z., Nilius, A.M., Mollison, K., Flamm, R.K. Antimicrob. Agents Chemother. (2001) [Pubmed]
  9. mefE is necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae. Tait-Kamradt, A., Clancy, J., Cronan, M., Dib-Hajj, F., Wondrack, L., Yuan, W., Sutcliffe, J. Antimicrob. Agents Chemother. (1997) [Pubmed]
  10. Antipneumococcal activity of ABT-773 compared to those of 10 other agents. Davies, T.A., Ednie, L.M., Hoellman, D.M., Pankuch, G.A., Jacobs, M.R., Appelbaum, P.C. Antimicrob. Agents Chemother. (2000) [Pubmed]
  11. In vitro selection of resistance to four beta-lactams and azithromycin in Streptococcus pneumoniae. Pankuch, G.A., Jueneman, S.A., Davies, T.A., Jacobs, M.R., Appelbaum, P.C. Antimicrob. Agents Chemother. (1998) [Pubmed]
  12. The emergence of Streptococcus pneumoniae resistant to macrolide antimicrobial agents: a 6-year population-based assessment. Gay, K., Baughman, W., Miller, Y., Jackson, D., Whitney, C.G., Schuchat, A., Farley, M.M., Tenover, F., Stephens, D.S. J. Infect. Dis. (2000) [Pubmed]
  13. In vitro development of resistance to telithromycin (HMR 3647), four macrolides, clindamycin, and pristinamycin in Streptococcus pneumoniae. Davies, T.A., Dewasse, B.E., Jacobs, M.R., Appelbaum, P.C. Antimicrob. Agents Chemother. (2000) [Pubmed]
 
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