ArticleAntimicrobial agents and chemotherapy2011
Induction of efflux-mediated macrolide resistance in Streptococcus pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Macrolide antibiotic action, resistance, and tolerance, and approaches to improve their activity against Gram-negative bacteria.The Journal of antibiotics · 2026Review
- Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review.Frontiers in pharmacology · 2024Review
- A Review of the Resistance Mechanisms forMedicina (Kaunas, Lithuania) · 2023Review
- The persistence and stabilization of auxiliary genes in the human skin virome.Virology journal · 2023Article
- Inducible Mega-Mediated Macrolide Resistance Confers Heteroresistance in Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2023Article
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Interactions of Aminopropyl-Azithromycin Derivatives, Precursors in the Synthesis of Bioactive Macrozones, withMaterials (Basel, Switzerland) · 2021Article
- The Role of Proteomics in Bacterial Response to Antibiotics.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics.The Journal of antibiotics · 2020Article
- High-Level Macrolide Resistance Due to the Mega Element [Frontiers in microbiology · 2019Article
- Identification and prioritization of macrolideresistance genes with hypothetical annotation inStreptococcus pneumoniae.Bioinformation · 2018Article
- Environmental and genetic modulation of the phenotypic expression of antibiotic resistance.FEMS microbiology reviews · 2017Review
- Resistance to Macrolide Antibiotics in Public Health Pathogens.Cold Spring Harbor perspectives in medicine · 2016Review
- Macrolide Resistance inFrontiers in cellular and infection microbiology · 2016Review
- Article
- Composite mobile genetic elements disseminating macrolide resistance in Streptococcus pneumoniae.Frontiers in microbiology · 2015Article
- Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance.Clinical microbiology reviews · 2012Review
- Acquired inducible antimicrobial resistance in Gram-positive bacteria.Future microbiology · 2012Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The antimicrobial efflux system encoded by the operon mef(E)-mel on the mobile genetic element MEGA in Streptococcus pneumoniae and other Gram-positive bacteria is inducible by macrolide antibiotics and antimicrobial peptides. Induction may affect the clinical response to the use of macrolides. We developed mef(E) reporter constructs and a disk diffusion induction and resistance assay to determine the kinetics and basis of mef(E)-mel induction. Induction occurred rapidly, with a >15-fold increase in transcription within 1 h of exposure to subinhibitory concentrations of erythromycin. A spectrum of environmental conditions, including competence and nonmacrolide antibiotics with distinct cellular targets, did not induce mef(E). Using 16 different structurally defined macrolides, induction was correlated with the amino sugar attached to C-5 of the macrolide lactone ring, not with the size (e.g., 14-, 15- or 16-member) of the ring or with the presence of the neutral sugar cladinose at C-3. Macrolides with a monosaccharide attached to C-5, known to block exit of the nascent peptide from the ribosome after the incorporation of up to eight amino acids, induced mef(E) expression. Macrolides with a C-5 disaccharide, which extends the macrolide into the ribosomal exit tunnel, disrupting peptidyl transferase activity, did not induce it. The induction of mef(E) did not require macrolide efflux, but the affinity of macrolides for the ribosome determined the availability for efflux and pneumococcal susceptibility. The induction of mef(E)-mel expression by inducing macrolides appears to be based on specific interactions of the macrolide C-5 saccharide with the ribosome that alleviate transcriptional attenuation of mef(E)-mel.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.