The presence of a novel macrolide efflux system in streptococci was first described and firmly established in 1996 by Sutcliffe et al. (81). This system was phenotypically recognized and characterized to confer low-level resistance (MICs, 1 to 32 μg/ml) to 14- and 15-membered macrolides but not to 16-membered macrolides, lincosamides, or streptogramin B (or their analogues). This phenotypic pattern of antibiotic resistance was referred to as M-type resistance and is in contrast to the MLSB phenotype, which confers constitutive high-level resistance (MICs, ≥256 μg/ml) to macrolides, lincosamides, as well as streptogramin B. In the same year Clancy et al. (16) identified the gene responsible for this novel efflux system in Streptococcus pyogenes, and it was designated mef(A). This gene was deposited in the public DNA databases and could be considered the reference sequence for the mef(A) gene (GenBank accession number U70055 ). Tait-Kamradt et al. (84) later identified a similar gene in Streptococcus pneumoniae that at the time was designated mef(E). Likewise, this gene could be considered the reference sequence for mef(E) (GenBank accession number U83667 ).
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Klaassen et al. (2005) studied this question.
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