ArticleScientific reports2017
A temporal proteome dynamics study reveals the molecular basis of induced phenotypic resistance in Mycobacterium smegmatis at sub-lethal rifampicin concentrations.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 29 citations in OpenAlex.
- Beyond Inhibition: Sublethal Rifampicin-Induced Molecular Adaptations Confer Phenotypic Drug Tolerance in Mycobacteria.ACS infectious diseases · 2026Article
- Proteomic Insights into Antimicrobial Resistance Mechanisms in Human-Associated Bacterial Pathogens.Microbial ecology · 2026Review
- Zoonotic Tuberculosis as a One Health Challenge: Global Evidence, Transmission Dynamics, and Policy Gaps in Indonesia.Veterinary sciences · 2026Review
- Comparative genomics and molecular characterization of a multidrug-resistant Corynebacterium glucuronolyticum isolated for the first time from the human genitourinary tract in Latin America.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026Article
- MoaB2, a newly identified transcription factor, binds to σJournal of bacteriology · 2024Article
- Temporal Profiling of Host Proteome against DifferentMicroorganisms · 2023Article
- What the Hel: recent advances in understanding rifampicin resistance in bacteria.FEMS microbiology reviews · 2023Article
- Mycobacterial Regulatory Systems Involved in the Regulation of Gene Expression Under Respiration-Inhibitory Conditions.Journal of microbiology (Seoul, Korea) · 2023Review
- Proteomic and metabolomic signatures of U87 glioblastoma cells treated with cisplatin and/or paclitaxel.Annals of medicine · 2023Article
- Myxopyronin B inhibits growth of a Fidaxomicin-resistant Clostridioides difficile isolate and interferes with toxin synthesis.Gut pathogens · 2022Article
- Mirror proteases of Ac-Trypsin and Ac-LysargiNase precisely improve novel event identifications inFrontiers in microbiology · 2022Article
- Dynamic Adaptive Response ofAntibiotics (Basel, Switzerland) · 2021Article
- Cell Wall Proteomics Reveal Phenotypic Adaption of Drug-ResistantFrontiers in medicine · 2021Article
- Monitoring protein communities and their responses to therapeutics.Nature reviews. Drug discovery · 2020Review
- Quantitative Proteomics of the 2016 WHOMolecular & cellular proteomics : MCP · 2019Article
- Associating HEmerging microbes & infections · 2018Article
- Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription.Nature communications · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the last 40 years only one new antitubercular drug has been approved, whilst resistance to current drugs, including rifampicin, is spreading. Here, we used the model organism Mycobacterium smegmatis to study mechanisms of phenotypic mycobacterial resistance, employing quantitative mass spectrometry-based proteomics to investigate the temporal effects of sub-lethal concentrations of rifampicin on the mycobacterial proteome at time-points corresponding to early response, onset of bacteriostasis and early recovery. Across 18 samples, a total of 3,218 proteins were identified from 31,846 distinct peptides averaging 16,250 identified peptides per sample. We found evidence that two component signal transduction systems (e.g. MprA/MprB) play a major role during initial mycobacterial adaptive responses to sub-lethal rifampicin and that, after dampening an initial SOS response, the bacteria supress the DevR (DosR) regulon and also upregulate their transcriptional and translational machineries. Furthermore, we found a co-ordinated dysregulation in haeme and mycobactin synthesis. Finally, gradual upregulation of the M. smegmatis-specific rifampin ADP-ribosyl transferase was observed which, together with upregulation of transcriptional and translational machinery, likely explains recovery of normal growth. Overall, our data indicates that in mycobacteria, sub-lethal rifampicin triggers a concerted phenotypic response that contrasts significantly with that observed at higher antimicrobial doses.
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