Transcriptional Attenuation Controls Macrolide Inducible Efflux and Resistance in Streptococcus pneumoniae and in Other Gram-Positive Bacteria Containing mef/mel(msr(D)) Elements

Macrolide resistance, emerging in Streptococcus pneumoniae and other Gram-positive bacteria, is increasingly due to efflux pumps encoded by mef/mel(msr) operons found on discrete mobile genetic elements. The regulation of mef/mel(msr) in these elements is not well understood. We identified the mef(E...

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Vydáno v:PloS one Ročník 10; číslo 2; s. e0116254
Hlavní autoři: Chancey, Scott T., Bai, Xianhe, Kumar, Nikhil, Drabek, Elliott F., Daugherty, Sean C., Colon, Thomas, Ott, Sandra, Sengamalay, Naomi, Sadzewicz, Lisa, Tallon, Luke J., Fraser, Claire M., Tettelin, Hervé, Stephens, David S.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 19.02.2015
Public Library of Science (PLoS)
Témata:
Anti-Bacterial Agents - pharmacology
Antibiotics
Attenuation
Bacteria
Bacterial infections
Chromosomes
Efflux
Gene expression
Genetic aspects
Genomes
Gram-positive bacteria
Gram-Positive Bacteria - drug effects
Guanine
Infectious diseases
Laboratories
Laws, regulations and rules
Macrolides - pharmacology
Medicine
Microbial drug resistance
Microbial Sensitivity Tests
mRNA stability
Operons
Pathogenesis
Pneumonia
Protein sorting signals
Protein structure
Purines
Regulatory mechanisms (biology)
Ribonucleic acid
RNA
Secondary structure
Streptococcus infections
Streptococcus pneumoniae
Streptococcus pneumoniae - drug effects
Streptococcus pyogenes
Streptococcus pyogenes - drug effects
Transcription
Transcription (Genetics)
Veterans
Atlanta Georgia
Georgia
United States > US
Maryland
Baltimore Maryland
ISSN:1932-6203, 1932-6203
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Popis
Shrnutí:Macrolide resistance, emerging in Streptococcus pneumoniae and other Gram-positive bacteria, is increasingly due to efflux pumps encoded by mef/mel(msr) operons found on discrete mobile genetic elements. The regulation of mef/mel(msr) in these elements is not well understood. We identified the mef(E)/mel transcriptional start, localized the mef(E)/mel promoter, and demonstrated attenuation of transcription as a mechanism of regulation of macrolide-inducible mef-mediated macrolide resistance in S. pneumoniae. The mef(E)/mel transcriptional start site was a guanine 327 bp upstream of mef(E). Consensus pneumococcal promoter -10 (5'-TATACT-3') and -35 (5'-TTGAAC-3') boxes separated by 17 bp were identified 7 bp upstream of the start site. Analysis of the predicted secondary structure of the 327 5' region identified four pairs of inverted repeats R1-R8 predicted to fold into stem-loops, a small leader peptide [MTASMRLR, (Mef(E)L)] required for macrolide induction and a Rho-independent transcription terminator. RNA-seq analyses provided confirmation of transcriptional attenuation. In addition, expression of mef(E)L was also influenced by mef(E)L-dependent mRNA stability. The regulatory region 5' of mef(E) was highly conserved in other mef/mel(msr)-containing elements including Tn1207.1 and the 5612IQ complex in pneumococci and Tn1207.3 in Group A streptococci, indicating a regulatory mechanism common to a wide variety of Gram-positive bacteria containing mef/mel(msr) elements.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: STC DSS. Performed the experiments: STC XB NK NS LS LJT TC SO. Analyzed the data: STC SD EFD HT DSS. Wrote the paper: STC HT DSS. Supervised sequencing and analysis activities: CMF.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0116254