ArticleAntimicrobial agents and chemotherapy2013
Aminoglycoside cross-resistance in Mycobacterium tuberculosis due to mutations in the 5' untranslated region of whiB7.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77 citing papers in PubMed, 143 citations in OpenAlex.
- Transcription attenuation amplifies collateral vulnerabilities in rifampicin-resistant Mycobacterium tuberculosis.Nature microbiology · 2026Article
- A Comprehensive Review of Genetic Mechanisms ofInfection and drug resistance · 2026Review
- Current and emerging therapies for pulmonary tuberculosis in adults.BMJ medicine · 2026Review
- Key resistance-associated mutations in multidrug-resistant tuberculosis: a genomic study from Shanghai, China, with a focus on aminoglycosides.BMC microbiology · 2025Article
- Advancing against drug-resistant tuberculosis: an extensive review, novel strategies and patent landscape.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- WhiB-like proteins: Diversity of structure, function and mechanism.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Drug-resistant tuberculosis: a persistent global health concern.Nature reviews. Microbiology · 2024Review
- Beyond antibiotic resistance: The whiB7 transcription factor coordinates an adaptive response to alanine starvation in mycobacteria.Cell chemical biology · 2024Article
- A virulence-associated small RNA MTS1338 activates an ABC transporter CydC for rifampicin efflux inFrontiers in microbiology · 2024Article
- Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation.RSC medicinal chemistry · 2023Review
- Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations.Scientific reports · 2023Article
- Beyond antibiotic resistance: thebioRxiv : the preprint server for biology · 2023Article
- Analysis of Genome-Wide Mutational Dependence in Naturally Evolving Mycobacterium tuberculosis Populations.Molecular biology and evolution · 2023Article
- Whole-genome sequencing and transcriptome-characterizedMicrobial genomics · 2023Article
- Article
- Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan.Scientific reports · 2023Article
- Discovery and Mechanistic Analysis of Structurally Diverse Inhibitors of Acetyltransferase Eis among FDA-Approved Drugs.Biochemistry · 2023Article
- The prevalence and distribution of aminoglycoside resistance genes.Biosafety and health · 2023Review
- The role ofFrontiers in cellular and infection microbiology · 2023Review
- Discovery and development of inhibitors of acetyltransferase Eis to combat Mycobacterium tuberculosis.Methods in enzymology · 2023Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since the discovery of streptomycin's bactericidal activity against Mycobacterium tuberculosis, aminoglycosides have been utilized to treat tuberculosis (TB). Today, the aminoglycosides kanamycin and amikacin are used to treat multidrug-resistant (MDR) TB, and resistance to any of the second-line injectable antibiotics, including kanamycin, amikacin, or capreomycin, is a defining characteristic of extensively drug-resistant (XDR) TB. Resistance to kanamycin and streptomycin is thought to be due to the acquisition of unlinked chromosomal mutations. However, we identified eight independent mutations in the 5' untranslated region of the transcriptional activator whiB7 that confer low-level resistance to both aminoglycosides. The mutations lead to 23- to 145-fold increases in whiB7 transcripts and subsequent increased expression of both eis (Rv2416c) and tap (Rv1258c). Increased expression of eis confers kanamycin resistance in these mutants, while increased expression of tap, which encodes an efflux pump, is a previously uncharacterized mechanism of low-level streptomycin resistance. Additionally, high-level resistance to streptomycin arose at a much higher frequency in whiB7 mutants than in a wild-type (WT) strain. Although whiB7 is typically associated with intrinsic antibiotic resistance in M. tuberculosis, these data suggest that mutations in an uncharacterized regulatory region of whiB7 contribute to cross-resistance against clinically used second-line antibiotics. As drug resistance continues to develop and spread, understanding the mechanisms and molecular basis of antibiotic resistance is critical for the development of rapid molecular tests to diagnose drug-resistant TB strains and ultimately for designing regimens to treat drug-resistant cases of TB.
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