Related Experiment Video
Updated: Sep 19, 2025
Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
Published on: January 5, 2024
Identification of Compounds With Potential Dual Inhibitory Activity Against Drug Efflux Pumps in Resistant Cancer
Elina Beleva1,2, Antonia Diukendjieva1, Ilza Pajeva1
1QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Background:
Drug efflux mediated by transporter proteins is one of the major mechanisms conferring multidrug resistance (MDR) to antimicrobial agents in bacteria and to chemotherapeutics in cancer cells. Therefore, the development or identification of efflux modulators represents a promising strategy to overcome the resistant phenotype. Various chemical compounds have been tested in experimental studies as reversal agents either in combination with antimicrobial or anticancer drugs and have shown sensitizing activity in resistant bacteria or cancer cell lines. Owing to the common resistance mechanisms exhibited by bacteria and cancer cells, the identification of chemical agents with dual reversal activity offers a strategy to simultaneously combat antibacterial and cancer multidrug resistance.
Objective:
This study aims to conduct a systematic review to identify compounds that have shown activity in reversing antibacterial as well as cancer MDR mediated by drug efflux pumps and to summarize their structural and biological parameters responsible for the interactions with drug efflux pumps.
Methods:
The protocol has been developed in accordance with PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guidelines. We searched PubMed and Scopus databases for abstracts of full-text peer-reviewed journal papers in English language published between January 2012 and September 2024. Only studies from in vitro experiments were considered if they used methods to detect changes in antibiotic sensitivity of resistant bacteria and chemosensitivity of resistant cancer cells upon treatment with efflux pump inhibitors. A total of 763 unique records were identified. Of them, 246 were selected for full-text review based on the eligibility criteria. Abstract screening was performed by 2 independent reviewers. As of March 1, 2025, the systematic review is at the stage of completed abstract screening. The next steps of the full-text review, study selection, data extraction, and risk of bias assessment will be performed by 2 independent reviewers as well. Main data elements will include a structural identifier of the tested inhibitor, bacterial strain, cancer cell line, methods proving reversal activity, half maximal inhibitory concentration, and other relevant quantitative estimates of reversal activity. Data synthesis will be performed as a narrative summary and the content will be curated in tabular and graphical form.
Results:
We anticipate that results from this study will outline the potential of various compounds to act as dual chemosensitizers and reverse both antimicrobial and cancer MDR.
Conclusions:
Our review will highlight the overlap between efflux pumps' inhibition as a strategy to combat MDR in both bacterial and cancer cells and it will provide structured data for rational drug design of dual efflux pump inhibitors.
Trial Registration:
PROSPERO CRD42024548350; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024548350.
International Registered Report Identifier (Irrid):
PRR1-10.2196/66197.
Insights
This systematic review identifies compounds that reverse multidrug resistance (MDR) in both bacteria and cancer cells. Findings will aid in designing dual efflux pump inhibitors to combat MDR effectively.
Area of Science:
- Pharmacology
- Molecular Biology
- Drug Discovery
Background:
- Multidrug resistance (MDR) in bacteria and cancer cells is often mediated by drug efflux pumps.
- Developing efflux pump inhibitors is a key strategy to overcome MDR.
- Identifying compounds with dual activity against both bacterial and cancer MDR is highly desirable.
Purpose of the Study:
- To systematically review compounds that reverse both antibacterial and cancer MDR.
- To identify structural and biological parameters influencing efflux pump interactions.
- To provide a foundation for rational drug design of dual efflux pump inhibitors.
Main Methods:
- Systematic review following PRISMA-P guidelines.
- Searched PubMed and Scopus databases (Jan 2012 - Sep 2024).
- Included in vitro studies assessing changes in sensitivity to antimicrobials and chemotherapeutics upon treatment with efflux pump inhibitors.
Main Results:
- Anticipate outlining potential dual-acting chemosensitizers.
- Results will highlight compounds capable of reversing both antimicrobial and cancer MDR.
- Data will be synthesized narratively and presented in tabular and graphical formats.
Conclusions:
- Efflux pump inhibition is a viable strategy for combating MDR in both bacteria and cancer.
- This review will underscore the overlap in resistance mechanisms.
- Structured data will facilitate the rational design of novel dual efflux pump inhibitors.
Related Concept Videos
02:56Treatment Resistant Cancers
01:27Combined Effects of Drugs: Synergism
Such synergistic combinations...