[Efflux-mediated antimicrobial multidrug resistance]

Agata Jarmuła1, Ewa Obłąk, Donata Wawrzycka

  • 1Instytut Genetyki i Mikrobiologii, Uniwersytet Wrocławski.

Insights

Multidrug resistance in infections stems from active drug efflux by bacterial and fungal proteins. Inhibitors are being developed to combat this challenge, which spreads via mobile genetic elements.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Context:

  • Multidrug resistance (MDR) poses a significant challenge in treating bacterial and fungal infections.
  • Active efflux of drugs by cellular pumps is a primary resistance mechanism.
  • Efflux pumps export a wide range of compounds, including antibiotics and antifungals.

Purpose:

  • To elucidate the mechanisms of multidrug resistance mediated by efflux pumps in bacteria and fungi.
  • To highlight the role of efflux pump proteins in drug export and resistance.
  • To discuss the genetic basis of resistance and potential therapeutic strategies.

Summary:

  • Bacterial multidrug resistance involves efflux pumps from five families (MF, SMR, ABC, RND, MATE) exporting diverse substrates.
  • Resistance genes on mobile elements facilitate rapid spread of multidrug resistance.
  • Fungal multidrug resistance also involves efflux pumps, notably the ABC superfamily's PDR subfamily, extensively studied in Saccharomyces cerevisiae.

Impact:

  • Understanding efflux pump function is crucial for developing novel antimicrobial therapies.
  • Targeting efflux pumps offers a strategy to overcome existing drug resistance.
  • Research into efflux pump inhibitors (EPIs) is vital for combating infectious diseases.

Related Concept Videos

Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Antimicrobial Effectiveness01:28

Antimicrobial Effectiveness

The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...