ArticleTuberculosis (Edinburgh, Scotland)2023
Mab2780c, a TetV-like efflux pump, confers high-level spectinomycin resistance in mycobacterium abscessus.
Article in Tuberculosis (Edinburgh, Scotland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- The Role of β-Lactam Antibiotics in Treating Mycobacterium abscessus: From Laboratory Insights to Clinical Applications and the Case for Clinical Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Review
- Article
- Prodrug florfenicol amine is activated by intrinsic resistance to target Mycobacterium abscessus.Nature microbiology · 2025Article
- Activity of combinations of bactericidal and bacteriostatic compounds inFrontiers in microbiology · 2025Review
- Synthesis and antibacterial action of 3',6'-disubstituted spectinomycins.The Journal of antibiotics · 2024Article
- Efflux pump effects on levofloxacin resistance inAntimicrobial agents and chemotherapy · 2024Article
- Development of 2nd generation aminomethyl spectinomycins that overcome native efflux inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring antibiotic resistance mechanisms inFrontiers in microbiology · 2024Review
- Hierarchy and interconnected networks in the WhiB7 mediated transcriptional response to antibiotic stress in Mycobacterium abscessus.PLoS genetics · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
Mycobacterium abscessus is highly resistant to spectinomycin (SPC) thereby making it unavailable for therapeutic use. Sublethal exposure to SPC strongly induces whiB7 and its regulon, and a ΔMab_whiB7 strain is SPC sensitive suggesting that the determinants of SPC resistance are included within its regulon. In the present study we have determined the transcriptomic changes that occur in M. abscessus upon SPC exposure and have evaluated the involvement of 11 genes, that are both strongly SPC induced and whiB7 dependent, in SPC resistance. Of these we show that MAB_2780c can complement SPC sensitivity of ΔMab_whiB7 and that a ΔMab_2780c strain is ∼150 fold more SPC sensitive than wildtype bacteria, but not to tetracycline (TET) or other aminoglycosides. This is in contrast to its homologues, TetV from M. smegmatis and Tap from M. tuberculosis, that confer low-level resistance to TET, SPC and other aminoglycosides. We also show that the addition of the efflux pump inhibitor (EPI), verapamil results in >100-fold decrease in MIC of SPC in bacteria expressing Mab2780c to the levels observed for ΔMab_2780c; moreover a deletion of MAB_2780c results in a decreased efflux of the drug into the cell supernatant. Together our data suggest that Mab2780c is an SPC antiporter. Finally, molecular docking of SPC and TET on models of TetV
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