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

• mefE is necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae [9].

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

• By 1999, 93% of the mefE-containing strains had minimum inhibitory concentrations >/=8 microgram/mL [12].

References