Multidrug efflux pumps: structure, function and regulation
Dijun Du1, Xuan Wang-Kan2, Arthur Neuberger1,3
1Department of Biochemistry, University of Cambridge, Cambridge, UK.
Abstract:
Infections arising from multidrug-resistant pathogenic bacteria are spreading rapidly throughout the world and threaten to become untreatable. The origins of resistance are numerous and complex, but one underlying factor is the capacity of bacteria to rapidly export drugs through the intrinsic activity of efflux pumps. In this Review, we describe recent advances that have increased our understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria. Clinical and laboratory data indicate that efflux pumps function not only in the drug extrusion process but also in virulence and the adaptive responses that contribute to antimicrobial resistance during infection. The emerging picture of the structure, function and regulation of efflux pumps suggests opportunities for countering their activities.
Insights
Multidrug-resistant bacterial infections are a growing threat. Understanding bacterial efflux pumps, which export drugs and contribute to resistance, offers new strategies to combat these infections.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Multidrug-resistant (MDR) bacterial infections pose a significant global health challenge, potentially rendering current treatments ineffective.
- A key mechanism enabling bacterial drug resistance is the activity of efflux pumps, which actively transport antimicrobial agents out of bacterial cells.
- Efflux pumps are intrinsic to bacteria and play a complex role in the development and spread of antimicrobial resistance.
Purpose of the Study:
- To review recent advancements in understanding the structure and molecular mechanisms of bacterial multidrug efflux pumps.
- To explore the multifaceted roles of efflux pumps beyond drug extrusion, including their involvement in bacterial virulence and adaptive resistance responses.
- To identify potential therapeutic strategies targeting efflux pump activity to overcome antimicrobial resistance.
Main Methods:
- Literature review of recent scientific publications on bacterial efflux pumps.
- Analysis of structural and mechanistic data related to multidrug efflux pumps.
- Synthesis of clinical and laboratory findings on efflux pump function in infection and resistance.
Main Results:
- Recent research has significantly enhanced the understanding of multidrug efflux pump structures and their molecular mechanisms in bacteria.
- Efflux pumps are implicated not only in drug extrusion but also in bacterial virulence and adaptive responses contributing to antimicrobial resistance.
- The detailed knowledge of efflux pump structure, function, and regulation provides a basis for developing novel therapeutic interventions.
Conclusions:
- Targeting bacterial efflux pumps presents a promising avenue for combating the escalating crisis of multidrug-resistant infections.
- Further research into the intricate mechanisms of efflux pumps can lead to the development of effective strategies to restore antimicrobial efficacy.
- Understanding efflux pump roles in virulence and adaptation is crucial for comprehensive approaches to antimicrobial resistance control.
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