ArticleAntimicrobial agents and chemotherapy2008
ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Molecular epidemiology of fluoroquinolone resistant Salmonella in Africa: A systematic review and meta-analysis.PloS one · 2018Pooled it
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- Proanthocyanidins inhibit methane emissions by interacting with methyl-coenzyme M reductase and reshaping rumen microbiome function.Microbiome · 2026Article
- A specific amount of RamA must be reached to trigger increased expression of AcrAB, enhance efflux, and confer multidrug resistance.Nucleic acids research · 2026Article
- Chitosan-dextran sulfate nanocapsules for enhanced tigecycline efficacy against non-typhoidal Salmonella enterica.Scientific reports · 2026Article
- Plasmid-borne transcriptional regulator RamAp modulatesFrontiers in microbiology · 2026Article
- Strain-dependent contribution of the AcrAB-TolC efflux pump toMicrobiology (Reading, England) · 2025Article
- Structure-guided discovery and validation of a potent RamR inhibitor targeting efflux-mediated multidrug resistance in Salmonella typhimurium.Folia microbiologica · 2025Article
- The molecular mechanisms of quinolone resistance in Salmonella: a review.Archives of microbiology · 2025Review
- EPS inhibitor treatment of Salmonella impacts evolution without selecting for resistance to biofilm inhibition.NPJ biofilms and microbiomes · 2025Article
- Antibiotic-induced stress responses in Gram-negative bacteria and their role in antibiotic resistance.The Journal of antimicrobial chemotherapy · 2025Review
- Antibiotic susceptibility ofOpen veterinary journal · 2025Article
- Phenotypic and genomic changes in entericmSphere · 2024Article
- Major primary bile salts repressFrontiers in microbiology · 2024Article
- Long-term exposure to food-grade disinfectants causes cross-resistance to antibiotics in Salmonella enterica serovar Typhimurium strains with different antibiograms and sequence types.Antimicrobial resistance and infection control · 2023Article
- Comparison of Antibacterial Activity of Phytochemicals against Common Foodborne Pathogens and Potential for Selection of Resistance.Microorganisms · 2023Article
- Bacterial defences: mechanisms, evolution and antimicrobial resistance.Nature reviews. Microbiology · 2023Review
- Emergence of two AcrB substitutions conferring multidrug resistance toAntimicrobial agents and chemotherapy · 2023Article
- Mapping direct and indirect MarA/SoxS/Rob/RamA regulons inMicrobiology (Reading, England) · 2023Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the sequenced genome of Salmonella enterica serovar Typhimurium strain LT2, an open reading frame (STM0580) coding for a putative regulatory protein of the TetR family is found upstream of the ramA gene. Overexpression of ramA results in increased expression of the AcrAB efflux pump and, consequently, multidrug resistance (MDR) in several bacterial species. The inactivation of the putative regulatory protein gene upstream of ramA in a susceptible serovar Typhimurium strain resulted in an MDR phenotype with fourfold increases in the MICs of unrelated antibiotics, such as quinolones/fluoroquinolones, phenicols, and tetracycline. The inactivation of this gene also resulted in a fourfold increase in the expression of ramA and a fourfold increase in the expression of the AcrAB efflux pump. These results indicated that the gene encodes a local repressor of ramA and was thus named ramR. In contrast, the inactivation of marR, marA, soxR, and soxS did not affect the susceptibilities of the strain. In quinolone- or fluoroquinolone-resistant strains of serovar Typhimurium overexpressing AcrAB, several point mutations which resulted in amino acid changes or an in-frame shift were identified in ramR; in addition, mutations interrupting ramR with an IS1 element were identified in high-level fluoroquinolone-resistant serovar Typhimurium DT204 strains. One serovar Typhimurium DT104 isolate had a 2-nucleotide deletion in the putative RamR binding site found upstream of ramA. These mutations were confirmed to play a role in the MDR phenotype by complementing the isolates with an intact ramR gene or by inactivating their respective ramA gene. No mutations in the mar or sox region were found in the strains studied. In conclusion, mutations in ramR appear to play a major role in the upregulation of RamA and AcrAB and, consequently, in the efflux-mediated MDR phenotype of serovar Typhimurium.
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