Microbial efflux pump inhibition: tactics and strategies

Area of Science:

• Microbiology
• Pharmacology
• Biochemistry

Background:

• Pathogenic microorganisms are developing multidrug resistance, diminishing the efficacy of traditional antimicrobials.
• Multidrug efflux systems (MES) are key mechanisms conferring resistance by actively transporting antimicrobial agents out of cells.
• Novel strategies are needed to overcome antimicrobial resistance and control infections.

Purpose of the Study:

• To explore the potential of multidrug efflux pump inhibitors (EPIs) as a strategy to combat antimicrobial resistance.
• To highlight the tactical elements and advancements in EPI discovery platforms.
• To emphasize the integration of various approaches for efficient EPI development.

Main Methods:

• Utilizing high-throughput screening (HTS) and bioassay-guided purification to identify promising EPIs.
• Leveraging advances in genomics, proteomics, and structural biology for understanding MES.
• Employing chemogenomics and chemoinformatics for data mining and virtual/physical HTS.

Main Results:

• Identification of numerous promising EPIs through diverse screening and purification strategies.
• Advancements in assay development and data accumulation facilitate a new era of EPI discovery.
• The synergistic platform shows translational potential beyond potentiating conventional antimicrobials.

Conclusions:

• EPIs represent a viable strategy to overcome multidrug resistance by inhibiting MES.
• Integrated discovery platforms combining chemogenomics and chemoinformatics accelerate the identification of novel EPI chemotypes.
• This approach is crucial for expediting the preclinical development of effective antimicrobial therapies.