Format

Send to

Choose Destination
PLoS One. 2015 Feb 19;10(2):e0116254. doi: 10.1371/journal.pone.0116254. eCollection 2015.

Transcriptional attenuation controls macrolide inducible efflux and resistance in Streptococcus pneumoniae and in other Gram-positive bacteria containing mef/mel(msr(D)) elements.

Author information

1
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America; Laboratories of Microbial Pathogenesis, Department of Veterans Affairs Medical Center, Atlanta, Georgia, United States of America.
2
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
3
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
4
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Abstract

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.

PMID:
25695510
PMCID:
PMC4335068
DOI:
10.1371/journal.pone.0116254
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center