ArticleAntimicrobial agents and chemotherapy2004
Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 144 citations in OpenAlex.
- Molecular Mechanisms Underlying Antimicrobial Resistance in Mycobacteria.International journal of molecular sciences · 2026Review
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
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- Peptidyl tRNA Hydrolase Is Required for Robust Prolyl-tRNA Turnover in Mycobacterium tuberculosis.mBio · 2023Article
- Variability ofAntibiotics (Basel, Switzerland) · 2022Review
- Antibiotic Resistance toAntibiotics (Basel, Switzerland) · 2022Review
- The Role of Phosphorylation and Acylation in the Regulation of Drug Resistance inBiomedicines · 2022Review
- RNA Expression Analysis of Mycobacterial Methyltransferases Genes in Different Resistant Strains of Mycobacterium tuberculosis.Iranian biomedical journal · 2022Article
- Alterations in molecular response of Mycobacterium tuberculosis against anti-tuberculosis drugs.Molecular biology reports · 2022Review
- Tuberculosis challenges: Resistance, co-infection, diagnosis, and treatment.European journal of microbiology & immunology · 2022Review
- Alternative approaches utilizing click chemistry to develop next-generation analogs of solithromycin.European journal of medicinal chemistry · 2022Article
- Crystal structure and functional analysis of mycobacterial erythromycin resistance methyltransferase Erm38 reveals its RNA-binding site.The Journal of biological chemistry · 2022Article
- Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- Synthesis, Biological Evaluation, and Computational Analysis of Biaryl Side-Chain Analogs of Solithromycin.ChemMedChem · 2021Article
- Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes againstACS infectious diseases · 2021Article
- Microevolution of Mycobacterium tuberculosis Subpopulations and Heteroresistance in a Patient Receiving 27 Years of Tuberculosis Treatment in Germany.Antimicrobial agents and chemotherapy · 2021Article
- HflX is a GTPase that controls hypoxia-induced replication arrest in slow-growing mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Mycobacterial HflX is a ribosome splitting factor that mediates antibiotic resistance.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intrinsic resistance of the Mycobacterium tuberculosis complex (MTC) to most antibiotics, including macrolides, is generally attributed to the low permeability of the mycobacterial cell wall. However, nontuberculous mycobacteria (NTM) are much more sensitive to macrolides than members of the MTC. A search for macrolide resistance determinants within the genome of M. tuberculosis revealed the presence of a sequence encoding a putative rRNA methyltransferase. The deduced protein is similar to Erm methyltransferases, which confer macrolide-lincosamide-streptogramin (MLS) resistance by methylation of 23S rRNA, and was named ErmMT. The corresponding gene, ermMT (erm37), is present in all members of the MTC but is absent in NTM species. Part of ermMT is deleted in some vaccine strains of Mycobacterium bovis BCG, such as the Pasteur strain, which lack the RD2 region. The Pasteur strain was susceptible to MLS antibiotics, whereas MTC species harboring the RD2 region were resistant to them. The expression of ermMT in the macrolide-sensitive Mycobacterium smegmatis and BCG Pasteur conferred MLS resistance. The resistance patterns and ribosomal affinity for erythromycin of Mycobacterium host strains expressing ermMT, srmA (monomethyltransferase from Streptomyces ambofaciens), and ermE (dimethyltransferase from Saccharopolyspora erythraea) were compared, and the ones conferred by ErmMT were similar to those conferred by SrmA, corresponding to the MLS type I phenotype. These results suggest that ermMT plays a major role in the intrinsic macrolide resistance of members of the MTC and could be the first example of a gene conferring resistance by target modification in mycobacteria.
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