ArticleJournal of bacteriology2014
Mutations in the primary sigma factor σA and termination factor rho that reduce susceptibility to cell wall antibiotics.
Article in Journal of bacteriology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Mutations in RNA polymerase that drive the emergence of antibiotic resistance.Current opinion in microbiology · 2026Review
- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- σMicrobiology spectrum · 2022Article
- Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessusAntimicrobial agents and chemotherapy · 2022Article
- Adaptation of Bacillus thuringiensis to Plant Colonization Affects Differentiation and Toxicity.mSystems · 2021Article
- Mastering the control of the Rho transcription factor for biotechnological applications.Applied microbiology and biotechnology · 2021Review
- Article
- A metabolic checkpoint protein GlmR is important for diverting carbon into peptidoglycan biosynthesis in Bacillus subtilis.PLoS genetics · 2018Article
- Transcription termination factor Rho and microbial phenotypic heterogeneity.Current genetics · 2018Review
- Adaptive Mutations in RNA Polymerase and the Transcriptional Terminator Rho Have Similar Effects on Escherichia coli Gene Expression.Molecular biology and evolution · 2017Article
- Expression of multiple Bacillus subtilis genes is controlled by decay of slrA mRNA from Rho-dependent 3' ends.Nucleic acids research · 2016Article
- Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Combinations of glycopeptides and β-lactams exert synergistic antibacterial activity, but the evolutionary mechanisms driving resistance to both antibiotics remain largely unexplored. By repeated subculturing with increasing vancomycin (VAN) and cefuroxime (CEF) concentrations, we isolated an evolved strain of the model bacterium Bacillus subtilis with reduced susceptibility to both antibiotics. Whole-genome sequencing revealed point mutations in genes encoding the major σ factor of RNA polymerase (sigA), a cell shape-determining protein (mreB), and the ρ termination factor (rho). Genetic-reconstruction experiments demonstrated that the G-to-C substitution at position 336 encoded by sigA (sigA(G336C)), in the domain that recognizes the -35 promoter region, is sufficient to reduce susceptibility to VAN and works cooperatively with the rho(G56C) substitution to increase CEF resistance. Transcriptome analyses revealed that the sigA(G336C) substitution has wide-ranging effects, including elevated expression of the general stress σ factor (σ(B)) regulon, which is required for CEF resistance, and decreased expression of the glpTQ genes, which leads to fosfomycin (FOS) resistance. Our findings suggest that mutations in the core transcriptional machinery may facilitate the evolution of resistance to multiple cell wall antibiotics.
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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.