Efflux Pump-mediated Antimicrobial Resistance: Mechanisms, Clinical Impact, and Emerging Inhibitory Approaches

Microbial efflux pumps play a critical role in AMR by facilitating the active export of harmful substances from inside the microbial cell to the external environment. These membrane proteins, which are commonly found in Gram-negative and Gram-positive bacteria as well as fungi, can function as part of single-component or multi-component systems. These proteins contribute to the innate tolerance of pathogens to toxic compounds, thereby enhancing their ability to survive antibiotic treatment particularly at infection sites where drug delivery is challenging, and in vivo antibiotic concentrations are low. By focusing on these pumps, novel therapeutic approaches to break up biofilms and improve the efficiency of antibiotic therapies may be available. In addition to contributing to drug resistance, efflux pumps also play a significant role in biofilm formation—an important factor in chronic infections. Developing a better comprehension of the processes that underlie the operation of efflux pumps, the effects of symmetric and asymmetric pumps.

Gaining a deeper understanding of the mechanisms underlying the efflux pumps function, the consequences of symmetric and asymmetric pumps, the factors that regulate their expression, and the development of efflux pump inhibitors is essential in the fight against AMR. Inhibiting efflux pumps represents a promising strategy to restore the effectiveness of existing antibiotics. Exploring the structure–function relationships and the molecular basis of membrane-associated transport systems—both influx and efflux—and their role in antimicrobial resistance will support the development of next-generation antimicrobial therapies.

This collection aims to showcase the latest research understanding efflux pump-mediated antimicrobial resistance, a critical and increasingly recognized mechanism by which microbes evade the effects of antibiotics.
It emphasizes the intricate molecular mechanisms underlying efflux pump function, including, but not limited to, the following sub-topics:

o Structural dynamics of membrane proteins involved in drug transport

o Biochemical pathways facilitating substrate recognition and expulsion

o Development of efflux pump inhibitors (EPIs)

o Combination therapies targeting efflux pumps

o Strategies targeting the regulatory networks and treatment failures

We welcome the following article types: Hypothesis & Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review.

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• Editorial
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• Hypothesis and Theory
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Antimicrobial Resistance (AMR), Antibiotic Resistance Mechanisms, Membrane Transport Proteins, Symmetric and Asymmetric transporters, Efflux Pump Inhibitors and Biofilm Formation, Alternative therapy, Genetic mechanisms of regulation of Efflux Pumps, Microbial efflux pumps

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.