ArticleThe Journal of antimicrobial chemotherapy2021
Mutant RNA polymerase can reduce susceptibility to antibiotics via ppGpp-independent induction of a stringent-like response.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Mutations in RNA polymerase that drive the emergence of antibiotic resistance.Current opinion in microbiology · 2026Review
- Evolutionary trajectories determine feasibility of collateral sensitivity-based antibiotic treatment strategies in critical bacterial pathogens.Communications biology · 2025Article
- Genetic and molecular studies of fitC4 and its suppressors fitA76* and fit95 in Escherichia coli.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Genetic and molecular characterization of fit95 mutation of Escherichia coli: evidence that fit95 is an allele of pheT.Archives of microbiology · 2024Article
- mSphere of Influence: Targeting bacterial signaling and metabolism to overcome antimicrobial resistance.mSphere · 2024Article
- Deep mutational scanning reveals the molecular determinants of RNA polymerase-mediated adaptation and tradeoffs.Nature communications · 2023Article
- The fitness cost of horizontally transferred and mutational antimicrobial resistance inFrontiers in microbiology · 2023Review
- Expression of the qepA1 gene is induced under antibiotic exposure.The Journal of antimicrobial chemotherapy · 2021Article
- Genomic Analysis of Ciprofloxacin-ResistantFrontiers in microbiology · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in RNA polymerase (RNAP) can reduce susceptibility to ciprofloxacin in Escherichia coli, but the mechanism of transcriptional reprogramming responsible is unknown. Strains carrying ciprofloxacin-resistant (CipR) rpoB mutations have reduced growth fitness and their impact on clinical resistance development is unclear.
objectivesTo assess the potential for CipRrpoB mutations to contribute to resistance development by estimating the number of distinct alleles. To identify fitness-compensatory mutations that ameliorate the fitness costs of CipRrpoB mutations. To understand how CipRrpoB mutations reprogramme RNAP.
methodsE. coli strains carrying five different CipRrpoB alleles were evolved with selection for improved fitness and characterized for acquired mutations, relative fitness and MICCip. The effects of dksA mutations and a ppGpp0 background on growth and susceptibility phenotypes associated with CipRrpoB alleles were determined.
resultsThe number of distinct CipRrpoB mutations was estimated to be >100. Mutations in RNAP genes and in dksA can compensate for the fitness cost of CipRrpoB mutations. Deletion of dksA reduced the MICCip for strains carrying CipRrpoB alleles. A ppGpp0 phenotype had no effect on drug susceptibility.
conclusionsCipRrpoB mutations induce an ppGpp-independent stringent-like response. Approximately half of the reduction in ciprofloxacin susceptibility is caused by an increased affinity of RNAP to DksA while the other half is independent of DksA. Stringent-like response activating mutations might be the most diverse class of mutations reducing susceptibility to antibiotics.
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