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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...
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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...
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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...

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[Decrease in bactericidal activity of ciprofloxacin in Salmonella mutants generated following repeated exposure to

L Cebrián1, J C Rodríguez, I Escribano

  • 1Servicio de Microbiología, Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Alicante.

Revista Espanola De Quimioterapia : Publicacion Oficial De La Sociedad Espanola De Quimioterapia
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Salmonella developed reduced susceptibility to fluoroquinolones, impacting ciprofloxacin

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Area of Science:

  • Microbiology and Infectious Diseases
  • Pharmacology and Drug Resistance

Background:

  • Fluoroquinolones are critical antibiotics for treating bacterial infections.
  • Emergence of antimicrobial resistance, particularly fluoroquinolone resistance in Salmonella, poses a significant public health threat.
  • Understanding the mechanisms of resistance is crucial for effective treatment strategies.

Purpose of the Study:

  • To investigate the development of reduced fluoroquinolone susceptibility in Salmonella.
  • To characterize genetic alterations, specifically in the gyrA gene, associated with this reduced susceptibility.
  • To determine the impact of these alterations on the bactericidal activity of ciprofloxacin.

Main Methods:

  • In vitro generation of Salmonella mutants through repeated exposure to subinhibitory fluoroquinolone concentrations.
  • Genetic characterization of the gyrA gene in the developed mutants.
  • Assessment of the change in bactericidal activity of ciprofloxacin against these mutants.

Main Results:

  • Salmonella mutants exhibiting reduced fluoroquinolone susceptibility were successfully generated.
  • Alterations in the gyrA gene were identified in these mutants.
  • A significant decrease in ciprofloxacin's bactericidal activity was observed in all mutants, most notably in those derived from nalidixic acid-resistant strains.

Conclusions:

  • Reduced susceptibility to fluoroquinolones in Salmonella is associated with gyrA gene alterations.
  • These genetic changes diminish the bactericidal efficacy of ciprofloxacin.
  • The findings may explain therapeutic failures in treating Salmonella infections with fluoroquinolones and highlight the importance of monitoring resistance.