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Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the
Abolfazl Dashtbani-Roozbehani1, Melissa H Brown1
1College of Science and Engineering, Flinders University, Bedford Park, SA 5042, Australia.
Abstract:
The increasing emergence of antimicrobial resistance in staphylococcal bacteria is a major health threat worldwide due to significant morbidity and mortality resulting from their associated hospital- or community-acquired infections. Dramatic decrease in the discovery of new antibiotics from the pharmaceutical industry coupled with increased use of sanitisers and disinfectants due to the ongoing COVID-19 pandemic can further aggravate the problem of antimicrobial resistance. Staphylococci utilise multiple mechanisms to circumvent the effects of antimicrobials. One of these resistance mechanisms is the export of antimicrobial agents through the activity of membrane-embedded multidrug efflux pump proteins. The use of efflux pump inhibitors in combination with currently approved antimicrobials is a promising strategy to potentiate their clinical efficacy against resistant strains of staphylococci, and simultaneously reduce the selection of resistant mutants. This review presents an overview of the current knowledge of staphylococcal efflux pumps, discusses their clinical impact, and summarises compounds found in the last decade from plant and synthetic origin that have the potential to be used as adjuvants to antibiotic therapy against multidrug resistant staphylococci. Critically, future high-resolution structures of staphylococcal efflux pumps could aid in design and development of safer, more target-specific and highly potent efflux pump inhibitors to progress into clinical use.
Insights
Antimicrobial resistance in staphylococci is a global threat. Targeting multidrug efflux pumps with novel inhibitors offers a promising strategy to restore antibiotic effectiveness against resistant bacterial infections.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Antimicrobial resistance in staphylococci poses a significant global health challenge, leading to severe infections.
- Decreased antibiotic discovery and increased disinfectant use, exacerbated by the COVID-19 pandemic, worsen antimicrobial resistance.
- Staphylococci employ resistance mechanisms, including multidrug efflux pumps, to evade antimicrobial agents.
Purpose of the Study:
- To review current knowledge on staphylococcal efflux pumps and their clinical impact.
- To summarize potential efflux pump inhibitors from plant and synthetic origins.
- To highlight the potential of efflux pump inhibitors as adjuvants in antibiotic therapy.
Main Methods:
- Literature review of staphylococcal efflux pumps.
- Analysis of compounds identified in the last decade with efflux pump inhibitory activity.
- Discussion of the role of efflux pump inhibitors in combating antimicrobial resistance.
Main Results:
- Staphylococcal multidrug efflux pumps are key to antimicrobial resistance.
- Various plant-derived and synthetic compounds show potential as efflux pump inhibitors.
- Combination therapy with efflux pump inhibitors and antibiotics can enhance efficacy and reduce resistance selection.
Conclusions:
- Efflux pump inhibitors are a promising strategy to combat multidrug-resistant staphylococci.
- Further research, including high-resolution structural studies, is needed to develop potent and specific inhibitors for clinical use.
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