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Related Concept Videos

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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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Related Experiment Video

Updated: Aug 16, 2025

Metabolic Profiling to Determine Bactericidal or Bacteriostatic Effects of New Natural Products using Isothermal Microcalorimetry
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Bicyclomycin Activity against Multidrug-Resistant Gram-Negative Pathogens.

Weijie Wang1, Xiaoli Zhu2,3, Huan Luo1

  • 1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China.

Microbiology Spectrum
|December 19, 2022
PubMed
Summary

The antibiotic bicyclomycin shows potential against multidrug-resistant Gram-negative infections when combined with doxycycline. This combination demonstrates enhanced bacterial killing and efficacy in treating infections caused by carbapenem-resistant Enterobacteriaceae, E. coli, and K. pneumoniae.

Keywords:
MIC distributionbicyclomycinlethal synergymultidrug-resistant Gram-negative bacteriamurine model of infection

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Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Antimicrobial resistance (AMR) is a growing global health threat, particularly for multidrug-resistant (MDR) Gram-negative pathogens.
  • Limited treatment options exist for MDR Gram-negative infections, necessitating novel therapeutic strategies.
  • Revisiting older antibiotics with unique mechanisms of action, like bicyclomycin, offers a promising avenue to combat AMR.

Purpose of the Study:

  • To evaluate the antimicrobial activity of bicyclomycin against clinical isolates of MDR Gram-negative bacteria.
  • To investigate the synergistic potential of bicyclomycin in combination with doxycycline against these pathogens.
  • To assess the in vivo efficacy of the bicyclomycin-doxycycline combination in a murine infection model.

Main Methods:

  • Minimum Inhibitory Concentrations (MICs) of bicyclomycin and other antibiotics were determined for over 100 MDR Gram-negative clinical isolates.
  • Checkerboard assays were employed to assess synergistic interactions between bicyclomycin and doxycycline.
  • A murine model of infection was used to evaluate the therapeutic efficacy of the combination treatment.

Main Results:

  • Bicyclomycin demonstrated good activity against carbapenem-resistant Enterobacteriaceae (CRE) and Escherichia coli, and moderate activity against Klebsiella pneumoniae.
  • Synergistic growth inhibition was observed with the combination of bicyclomycin and doxycycline (FIC index <0.5).
  • The combination exhibited synthetic lethality against K. pneumoniae, achieving 100- to 1,000-fold greater bacterial killing than either agent alone, and showed improved efficacy in a murine model.

Conclusions:

  • Bicyclomycin possesses significant bacteriostatic and bactericidal activity against key MDR Gram-negative pathogens when used in combination with doxycycline.
  • The bicyclomycin-doxycycline combination represents a potential new therapeutic option for systemic MDR Gram-negative infections, including those caused by CRE, E. coli, and K. pneumoniae.
  • This study supports the expanded use of bicyclomycin beyond its traditional indications for treating challenging Gram-negative bacterial infections.