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Characterization and prevalence of MefA, MefE, and the associated msr(D) gene in Streptococcus pneumoniae clinical
Melissa M Daly1, Stella Doktor, Robert Flamm
1Infectious Disease Research, Abbott Laboratories, Bldg. AP52, 200 Abbott Park Rd., Abbott Park, IL 60064, USA.
Abstract:
Recent work has shown that the efflux genes in Streptococcus pneumoniae that are responsible for acquired macrolide resistance can be distinguished as either mef(E) or mef(A). The genetic elements on which mef(A) and mef(E) are found also carry an open reading frame (ORF) that is 56% homologous to msr(A) in Staphylococcus. The prevalence of mef(A/E) and of the msr-like ORF [msr(D)] was evaluated in 153 mef(+) S. pneumoniae clinical isolates collected in North America, Europe, Africa, and Asia from 1997 to 2002. Clinical isolates were screened with PCR primers specific for either mef(A) or mef(E) and for msr(D). mef(A), mef(E), and msr(D) were cloned from mef(+) strains and transformed into a susceptible, competent strain of S. pneumoniae. The transformants were tested for antimicrobial susceptibilities and efflux pump induction. The results of this work demonstrated that mef(A) is more often isolated in parts of Europe, with some incidence in Canada, and that the msr-like gene alone can confer the efflux phenotype.
Insights
The msr(D) gene in Streptococcus pneumoniae, similar to Staphylococcus msr(A), can independently confer macrolide resistance. This efflux gene was prevalent in clinical isolates, particularly mef(A) in Europe.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Acquired macrolide resistance in Streptococcus pneumoniae is mediated by efflux genes, specifically mef(E) or mef(A).
- These genes are often found on genetic elements that also contain a homologous open reading frame (ORF) to Staphylococcus msr(A), termed msr(D).
Purpose of the Study:
- To evaluate the prevalence of mef(A/E) and the msr(D) gene in clinical isolates of Streptococcus pneumoniae.
- To determine if the msr(D) gene alone can confer the macrolide efflux phenotype.
Main Methods:
- Screening of 153 mef(+) Streptococcus pneumoniae clinical isolates from diverse global regions (1997-2002) using PCR for mef(A), mef(E), and msr(D).
- Cloning of mef(A), mef(E), and msr(D) from resistant strains and transformation into a susceptible Streptococcus pneumoniae strain.
- Testing antimicrobial susceptibilities and efflux pump induction in transformants.
Main Results:
- The mef(A) gene was more frequently isolated in European isolates, with some presence in Canada.
- The msr(D) gene was found to confer the macrolide efflux phenotype independently.
- The study identified geographical variations in the prevalence of mef(A/E) genes.
Conclusions:
- The msr(D) gene is a significant contributor to macrolide resistance in Streptococcus pneumoniae.
- Understanding the distribution and function of these efflux genes is crucial for antimicrobial resistance surveillance.
- Targeting these efflux mechanisms could be a strategy to combat macrolide-resistant Streptococcus pneumoniae infections.
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