title: Membrane permeabilization of colistin toward pan-drug resistant Gram-negative isolates.
abstract: Pan-drug resistant Gram-negative bacteria, being resistant to most available antibiotics, represent a huge threat to the medical community. Colistin is considered the last therapeutic option for patients in hospital settings. Thus, we were concerned in this study to demonstrate the membrane permeabilizing activity of colistin focusing on investigating its efficiency toward those pan-drug resistant isolates which represent a critical situation. We determined the killing dynamics of colistin against pan-drug resistant isolates. The permeability alteration was confirmed by different techniques as: leakage, electron microscopy and construction of an artificial membrane model; liposomes. Moreover, selectivity of colistin against microbial cells was also elucidated. Colistin was proved to be rapid bactericidal against pan-drug resistant isolates. It interacts with the outer bacterial membrane leading to deformation of its outline, pore formation, leakage of internal contents, cell lysis and finally death. Furthermore, variations in membrane composition of eukaryotic and microbial cells provide a key for colistin selectivity toward bacterial cells. Colistin selectively alters membrane permeability of pan-drug resistant isolates which leads to cell lysis. Colistin was proved to be an efficient last line treatment for pan-drug resistant infections which are hard to treat.
authors.affiliation: Pharmaceutical Microbiology Department, Faculty of Pharmacy, Alexandria University, Egypt. Electronic address: ymohamed01@qub.ac.uk.
authors.forename: Yasmine Fathy
authors.initials: YF
authors.lastname: Mohamed
authors.affiliation: Pharmaceutical Microbiology Department, Faculty of Pharmacy, Alexandria University, Egypt.
authors.forename: Hamida Moustafa
authors.initials: HM
authors.lastname: Abou-Shleib
authors.affiliation: Pharmaceutical Microbiology Department, Faculty of Pharmacy, Alexandria University, Egypt.
authors.forename: Amal Mohamed
authors.initials: AM
authors.lastname: Khalil
authors.affiliation: Pharmaceutical Microbiology Department, Faculty of Pharmacy, Alexandria University, Egypt.
authors.forename: Nadia Mohamed
authors.initials: NM
authors.lastname: El-Guink
authors.affiliation: Pharmaceutical Microbiology Department, Faculty of Pharmacy, Alexandria University, Egypt.
authors.forename: Moustafa Ahmed
authors.initials: MA
authors.lastname: El-Nakeeb
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003091:Colistin / Q000378:metabolism* / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: Colistin; Leakage; Pan-drug resistant; Permeability alteration; Ultrastructure