Unlocking the Gates: A Novel Diagnostic Molecule for Quantifying Efflux Levels in Gram‐Positive Bacteria
Abstract
Efflux-mediated antibiotic resistance poses a significant global threat, affecting diverse bacterial species. Clinicians recognize the danger of efflux mechanisms during antibiotic treatment, yet precise diagnostic tools remain unavailable. The antibiogram currently infers abnormal efflux pump activity in clinical isolates, which is subsequently confirmed through transcriptomic or genomic analysis. This study harnesses the colorimetric, fluorescence, and solubility properties of phenazinium derivatives to develop a rapid protocol for detecting bacterial efflux. Among several synthesized phenazinium compounds, the compound demonstrating differential MIC in Staphylococcus efflux mutants and exhibiting appropriate physicochemical properties is selected. A diagnostic protocol is developed using the selected compound to assess efflux levels, categorized as no, weak, or strong, through colorimetry and spectroscopy techniques. Testing on Gram-positive efflux mutants and clinical Staphylococcus isolates further validates the approach. In-silico docking analysis confirms the interaction between the chosen compound and the NorA efflux pump in S. aureus. Flow cytometry is employed to re-evaluate the detection assays. The developed molecule and protocol represent the first known method to evaluate efflux levels in any Gram-positive species through a streamlined and user-friendly process. This pioneering test significantly advances the epidemiological analysis of efflux mechanisms and…
Read the paper
Related studies
- Structural and topological analysis of thiosemicarbazone-based metal complexes: computational and experimental study of bacterial biofilm inhibition and antioxidant activity
- Toward better cures for Mycobacterium abscessus lung disease
- Challenges for global antibiotic regimen planning and establishing antimicrobial resistance targets: implications for the WHO Essential Medicines List and AWaRe antibiotic book dosing
- Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3‐Triazoles: A Computational Docking Techniques
- Upregulation of pmrA, pmrB, pmrC, phoQ, phoP, and arnT genes contributing to resistance to colistin in superbug Klebsiella pneumoniae isolates from human clinical samples in Tehran, Iran
- Whole-genome sequencing of clinical isolates of Citrobacter Europaeus in China carrying blaOXA−48 and blaNDM−1
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.