ArticleScientific reports2019
Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Acquired mutations in transcriptional regulatorAntimicrobial agents and chemotherapy · 2026Article
- Correlation of type 3 secretion system genes with antimicrobial resistance inJournal of Taibah University Medical Sciences · 2026Article
- From Phenotype to Genotype: A Clonal Perspective on Virulence and Biofilm Formation in Bloodstream-DerivedInfection and drug resistance · 2026Article
- RND efflux pump inhibitor-like natural products as antibiotic adjuvants against multidrug-resistant gram-negative bacteria: a graded-evidence review.Frontiers in microbiology · 2026Review
- β,β-Dimethylacrylalkannin Restores Colistin Efficacy AgainstAntibiotics (Basel, Switzerland) · 2025Article
- Human vaginal Lactobacillus Jensenii -derived (-)-Terpinen-4-ol restores antibiotic sensitivity by inhibiting efflux pumps in drug resistant E. coli and K. pneumoniae.Scientific reports · 2025Article
- Matrine Restores Colistin Efficacy AgainstMolecules (Basel, Switzerland) · 2025Article
- Evolution of extended-spectrum β-lactamase-producing ST131 Escherichia coli at a single hospital over 15 years.Scientific reports · 2024Article
- Resistome Analysis ofMicroorganisms · 2024Article
- Allosteric-Regulation-Based DNA Circuits in Saccharomyces cerevisiae to Detect Organic Acids and Monitor Hydrocarbon Metabolism In Vitro.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Genome analysis of triple phages that curtails MDR E. coli with ML based host receptor prediction and its evaluation.Scientific reports · 2023Article
- Evolution of extended-spectrum β-lactamase-producing ST131bioRxiv : the preprint server for biology · 2023Article
- Role of efflux pumps, their inhibitors, and regulators in colistin resistance.Frontiers in microbiology · 2023Review
- An efflux-susceptible antibiotic-adjuvant with systemic efficacy against mouse infections.Scientific reports · 2022Article
- Rescuing humanity by antimicrobial peptides against colistin-resistant bacteria.Applied microbiology and biotechnology · 2022Review
- Dynamic Boolean modelling reveals the influence of energy supply on bacterial efflux pump expression.Journal of the Royal Society, Interface · 2022Article
- Colistin Resistance and Management of Drug Resistant Infections.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Review
- Unique mechanistic insights into pathways associated with the synergistic activity of polymyxin B and caspofungin against multidrug-resistantComputational and structural biotechnology journal · 2022Article
- Bacteriophage as a Novel Therapeutic Weapon for Killing Colistin-Resistant Multi-Drug-Resistant and Extensively Drug-Resistant Gram-Negative Bacteria.Current microbiology · 2021Review
- Colistin resistance in Gram-negative bacteria analysed by five phenotypic assays and inference of the underlying genomic mechanisms.BMC microbiology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibiotics like colistin are the last resort to deal with infections by carbapenem-resistant Enterobacteriaceae (CREB). Resistance to colistin severely restricts therapeutic options. To tackle this dire situation, urgent measures to restore colistin sensitivity are needed. In this study, whole-genome sequencing of colistin-resistant E. coli strain was performed and the genome analysis revealed that the strain belonged to the sequence type ST405. Multiple mutations were observed in genes implicated in colistin resistance, especially those related to the L-Ara-4-N pathway but mgrB was unmutated and mcr1-9 genes were missing. MarR inhibitor salicylate was used to re-sensitize this strain to colistin, which increased the negative charge on the cell surface especially in colistin resistant E. coli (U3790 strain) and thereby facilitated a decrease in colistin MIC by 8 fold. It is indeed well known that MarR inhibition by salicylate triggers the expression of AcrAB efflux pumps through MarA. So, in order to fully restore colistin sensitivity, a potent efflux pump inhibitor (BC1), identified earlier by this group was employed. The combination of colistin with both salicylate and BC1 caused a remarkable 6 log reduction in cell counts of U3790 in time-kill assay. Infection of muscle tissue of zebrafish with U3790 followed by various treatments showed that the combination of colistin + salicylate + BC1 was highly effective in reducing bioburden in infected muscle tissue by 4 log fold. Thus, our study shows that a combination of MarR inhibitor to enhance colistin binding and efflux pump inhibitor to reduce colistin extrusion was highly effective in restoring colistin sensitivity in colistin-resistant clinical isolate of E. coli in vitro and in vivo.
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