ArticleThe Journal of antimicrobial chemotherapy2014
RamA, which controls expression of the MDR efflux pump AcrAB-TolC, is regulated by the Lon protease.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
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- A specific amount of RamA must be reached to trigger increased expression of AcrAB, enhance efflux, and confer multidrug resistance.Nucleic acids research · 2026Article
- Exploring the principles behind antibiotics with limited resistance.Nature communications · 2025Article
- ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.Nature microbiology · 2025Article
- The investigation of molecular epidemiological characteristics and resistance mechanism of tigecycline resistantFrontiers in cellular and infection microbiology · 2025Article
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- Occurrence and mechanisms of tigecycline resistance in carbapenem- and colistin-resistant Klebsiella pneumoniae in Thailand.Scientific reports · 2024Article
- The Mar, Sox, and Rob Systems.EcoSal Plus · 2023Review
- EnvR is a potent repressor of acrAB transcription in Salmonella.The Journal of antimicrobial chemotherapy · 2022Article
- New Insights into the Mechanism of Antibacterial Action of Synthetic PeptideAntibiotics (Basel, Switzerland) · 2022Article
- Development of Resistance to Eravacycline by Klebsiella pneumoniae and Collateral Sensitivity-Guided Design of Combination Therapies.Microbiology spectrum · 2022Article
- Transcriptional Regulation and Functional Characterization of the Plasmid-BorneMicrobiology spectrum · 2022Article
- Serratia marcescens RamA Expression Is under PhoP-Dependent Control and Modulates Lipid A-Related Gene Transcription and Antibiotic Resistance Phenotypes.Journal of bacteriology · 2021Article
- Time dependent asymptotic analysis of the gene regulatory network of the AcrAB-TolC efflux pump system in gram-negative bacteria.Journal of mathematical biology · 2021Article
- The Formation of Two Hybrid Plasmids Mediated by ISFrontiers in microbiology · 2021Article
- Contribution of Different Mechanisms to Ciprofloxacin Resistance inFrontiers in microbiology · 2021Article
- Molecular epidemiology and mechanisms of tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae isolates.Journal of clinical laboratory analysis · 2020Article
- Amidochelocardin Overcomes Resistance Mechanisms Exerted on Tetracyclines and Natural Chelocardin.Antibiotics (Basel, Switzerland) · 2020Article
- Effect of rpoE on the Non-coding RNA Expression Profiles of Salmonella enterica serovar Typhi under the Stress of Ampicillin.Current microbiology · 2020Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
objectivesRamA regulates the AcrAB-TolC multidrug efflux system. Using Salmonella Typhimurium, we investigated the stability of RamA and its impact on antibiotic resistance.
methodsTo detect RamA, we introduced ramA::3XFLAG::aph into plasmid pACYC184 and transformed this into Salmonella Typhimurium SL1344ramA::cat and lon::aph mutants. An N-terminus-deleted mutant [pACYC184ramA(Δ2-21)::3XFLAG::aph] in which the first 20 amino acids of RamA were deleted was also constructed. To determine the abundance and half-life of FLAG-tagged RamA, we induced RamA with chlorpromazine (50 mg/L) and carried out western blotting using anti-FLAG antibody. Susceptibility to antibiotics and phenotypic characterization of the lon mutant was also carried out.
resultsWe show that on removal of chlorpromazine, a known inducer of ramA, the abundance of RamA decreased to pre-induced levels. However, in cells lacking functional Lon, we found that the RamA protein was not degraded. We also demonstrated that the 21 amino acid residues of the RamA N-terminus are required for recognition by the Lon protease. Antimicrobial susceptibility and phenotypic tests showed that the lon mutant was more susceptible to fluoroquinolone antibiotics, was filamentous when observed by microscopy and grew poorly, but showed no difference in motility or the ability to form a biofilm. There was also no difference in the ability of the lon mutant to invade human intestinal cells (INT-407).
conclusionsIn summary, we show that the ATP-dependent Lon protease plays an important role in regulating the expression of RamA and therefore multidrug resistance via AcrAB-TolC in Salmonella Typhimurium.
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