ArticleMicrobiology spectrum2023
Mechanism of Action of Isopropoxy Benzene Guanidine against Multidrug-Resistant Pathogens.
Article in Microbiology spectrum, 2023. 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, 17 citations in OpenAlex.
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- Preclinical evaluation of repositioned non-antibiotic agents against Staphylococcus aureus: a network meta-analysis of survival outcomes.World journal of microbiology & biotechnology · 2025Article
- IncI2 plasmid transfer and changes of intestinal microbiota in mice under β-lactam antibiotic pressure.BMC veterinary research · 2025Article
- Bavachin Rejuvenates Sensitivity of Colistin against Colistin-Resistant Gram-Negative Bacteria.International journal of molecular sciences · 2024Article
- Development of Novel Membrane Disrupting Lipoguanidine Compounds Sensitizing Gram-Negative Bacteria to Antibiotics.ACS medicinal chemistry letters · 2024Article
- Polymyxins: recent advances and challenges.Frontiers in pharmacology · 2024Review
- Fingolimod synergizes and reversesFrontiers in microbiology · 2024Article
- The synergistic antibacterial activity and mechanism of colistin-oxethazaine combination against gram-negative pathogens.Frontiers in pharmacology · 2024Article
- Antibacterial activity of isopropoxy benzene guanidine againstFrontiers in pharmacology · 2024Article
- Evaluating the Antibacterial and Antivirulence Activities of Floxuridine againstInternational journal of molecular sciences · 2023Article
- Metabolite Identification of Isopropoxy Benzene Guanidine in Rat Liver Microsomes by Using UHPLC-Q-TOF-MS/MS.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increasing emergence of antibiotic resistance is an urgent threat to global health care; thus, there is a need for new therapeutics. Guanidine is the preferred functional group for antimicrobial design and development. Herein, the potential antibacterial activity of the guanidine derivative isopropoxy benzene guanidine (IBG) against multidrug-resistant (MDR) bacteria was discovered. The synergistic antibacterial activity of IBG and colistin was determined by checkerboard assay, time-killing curve, and mouse experiments. The antibacterial mechanism of IBG was verified in fluorescent probe experiments, intracellular oxidative phosphorylation assays, and transcriptome analysis. The results showed that IBG displays efficient antibacterial activity against Gram-positive pathogens and Gram-negative pathogens with permeabilized outer membranes. Further mechanistic studies showed that IBG triggers cytoplasmic membrane damage by binding to phosphatidylglycerol and cardiolipin, leading to the dissipation of proton motive force and accumulation of intracellular ATP. IBG combined with low levels of colistin enhances bacterial outer membrane permeability and increases the accumulation of reactive oxygen species, as further evidenced by transcriptome analysis. Furthermore, the efficacy of IBG with colistin against MDR Escherichia coli in three infection models was demonstrated. Together, these results suggest that IBG is a promising adjuvant of colistin, providing an alternative approach to address the prevalent infections caused by MDR Gram-negative pathogens.
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Registered trials
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