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Membrane permeabilization of colistin toward pan-drug resistant Gram-negative isolates

Yasmine Fathy Mohamed1, Hamida Moustafa Abou-Shleib1, Amal Mohamed Khalil1

  • 1Pharmaceutical Microbiology Department, Faculty of Pharmacy, Alexandria University, Egypt.

Brazilian Journal of Microbiology : [Publication of the Brazilian Society for Microbiology]
|March 19, 2016
PubMed

Insights

Colistin rapidly kills pan-drug resistant Gram-negative bacteria by disrupting their cell membranes. This last-resort antibiotic offers a vital treatment option for critical infections due to its selective membrane permeabilizing activity.

Area of Science:

  • Microbiology
  • Bacteriology
  • Pharmacology

Background:

  • Pan-drug resistant Gram-negative bacteria pose a significant global health threat.
  • Colistin is a critical last-line antibiotic for treating infections caused by these resistant pathogens.

Purpose of the Study:

  • To investigate the membrane permeabilizing activity and bactericidal efficacy of colistin against pan-drug resistant Gram-negative bacteria.
  • To elucidate the mechanism of colistin's action, including its selectivity towards microbial cells.

Main Methods:

  • Determination of colistin's killing dynamics against resistant isolates.
  • Assessment of membrane permeability alterations using leakage assays, electron microscopy, and liposome-based artificial membrane models.
  • Elucidation of colistin's selectivity based on differences in eukaryotic and microbial cell membrane composition.

Main Results:

  • Colistin demonstrated rapid bactericidal activity against pan-drug resistant Gram-negative bacteria.
  • Colistin induced outer membrane deformation, pore formation, leakage of cellular contents, and cell lysis.
  • Colistin exhibited selectivity for bacterial cells over eukaryotic cells, attributed to membrane composition variations.

Conclusions:

  • Colistin effectively disrupts the membrane integrity of pan-drug resistant Gram-negative bacteria, leading to rapid cell death.
  • The selective action of colistin on bacterial membranes makes it a crucial therapeutic agent for challenging infections.
Keywords:
ColistinLeakagePan-drug resistantPermeability alterationUltrastructure

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