A multidrug efflux pump inhibitor reduces fluoroquinolone resistance in Pseudomonas aeruginosa isolates

Ahmet Yilmaz Coban1, Bora Ekinci, Belma Durupinar

  • 1Ondokuz Mayis University, Medical School, Department of Microbiology and Clinical Microbiology, Samsun, Turkey. ayilmazc@omu.edu.tr

Chemotherapy
|April 16, 2004
PubMed

Insights

Multidrug efflux pump inhibitor MC-207,110 significantly reduced fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa. This finding suggests MC-207,110 could be a valuable addition to clinical protocols for combating FQ resistance.

Area of Science:

  • Microbiology
  • Pharmacology
  • Molecular Biology

Background:

  • Antibiotic resistance is a growing threat, particularly in Gram-negative bacteria.
  • Fluoroquinolone (FQ) resistance mechanisms include target mutations and active efflux.
  • Reduced porin expression is also implicated in FQ resistance.

Purpose of the Study:

  • To investigate the interaction between FQs (levofloxacin, ofloxacin, ciprofloxacin) and the multidrug efflux pump inhibitor MC-207,110.
  • To assess the efficacy of MC-207,110 in overcoming FQ resistance in Pseudomonas aeruginosa.

Main Methods:

  • Checkerboard assay was employed using Pseudomonas aeruginosa.
  • Tested FQs at concentrations ranging from 0.06-64 µg/ml.
  • Tested MC-207,110 at concentrations ranging from 4-128 µg/ml.

Main Results:

  • MC-207,110 significantly inhibited FQ resistance and decreased Minimum Inhibitory Concentrations (MICs) at concentrations of 16-128 µg/ml.
  • The inhibitory effect was observed across levofloxacin, ofloxacin, and ciprofloxacin.
  • No significant inhibition was noted at lower MC-207,110 concentrations (4 and 8 µg/ml).

Conclusions:

  • MC-207,110 effectively inhibits FQ resistance in Pseudomonas aeruginosa in vitro.
  • MC-207,110 demonstrates potential as a therapeutic agent to overcome FQ resistance.
  • Further clinical studies are warranted to explore the utility of MC-207,110 in treatment protocols.

Related Concept Videos

Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
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...
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
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...
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...