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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 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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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...
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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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Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
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Quinolone resistance: much more than predicted.

Alvaro Hernández1, María B Sánchez, José L Martínez

  • 1Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología CSIC, Madrid, Spain.

Frontiers in Microbiology
|June 21, 2011
PubMed
Summary

Quinolone resistance emerges through more than just target gene mutations. Resistance genes, found in plasmids and originating in aquatic bacteria, can transfer, highlighting risks in non-clinical antibiotic use.

Keywords:
MDR efflux pumpqnrquinolone inactivationquinolone resistancetransfer of quinolone resistance

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Area of Science:

  • Microbiology
  • Genetics
  • Pharmacology

Background:

  • Quinolones are synthetic antibiotics.
  • Resistance was initially predicted to arise solely from target gene mutations.
  • However, diverse resistance mechanisms have been identified.

Purpose of the Study:

  • To investigate the mechanisms of quinolone resistance beyond target gene mutations.
  • To explore the transferability and reservoirs of quinolone resistance genes.
  • To assess the risks associated with non-clinical quinolone use.

Main Methods:

  • Review of existing literature on quinolone resistance mechanisms.
  • Analysis of genetic elements contributing to resistance (efflux pumps, protective proteins, modifying enzymes).
  • Investigation of plasmid-mediated resistance and gene origins.

Main Results:

  • Quinolone resistance is mediated by efflux pumps, target-protecting proteins, and modifying enzymes.
  • Some resistance elements are plasmid-encoded, enabling horizontal gene transfer.
  • Quinolone resistance (qnr) genes originate in aquatic bacteria, with potential for transfer via plasmids.

Conclusions:

  • Quinolone resistance is more complex than initially predicted.
  • Non-clinical environments, like fish farming, pose risks for resistance emergence.
  • Biological systems' plasticity necessitates considering diverse resistance pathways for future predictions.