NDLI: Membrane-active mechanism of LFchimera against Burkholderia pseudomallei and Burkholderia thailandensis

Content Provider	Springer Nature Link
Author	Kanthawong, Sakawrat Puknun, Aekkalak Bolscher, Jan G. M. Nazmi, Kamran Marle, Jan Soet, Johannes J. Veerman, En C. I. Wongratanacheewin, Surasakdi Taweechaisupapong, Suwimol
Copyright Year	2014
Abstract	LFchimera, a construct combining two antimicrobial domains of bovine lactoferrin, lactoferrampin265–284 and lactoferricin17–30, possesses strong bactericidal activity. As yet, no experimental evidence was presented to evaluate the mechanisms of LFchimera against Burkholderia isolates. In this study we analyzed the killing activity of LFchimera on the category B pathogen Burkholderia pseudomallei in comparison to the lesser virulent Burkholderia thailandensis often used as a model for the highly virulent B. pseudomallei. Killing kinetics showed that B. thailandensis E264 was more susceptible for LFchimera than B. pseudomallei 1026b. Interestingly the bactericidal activity of LFchimera appeared highly pH dependent; B. thailandensis killing was completely abolished at and below pH 6.4. FITC-labeled LFchimera caused a rapid accumulation within 15 min in the cytoplasm of both bacterial species. Moreover, freeze-fracture electron microscopy demonstrated extreme effects on the membrane morphology of both bacterial species within 1 h of incubation, accompanied by altered membrane permeability monitored as leakage of nucleotides. These data indicate that the mechanism of action of LFchimera is similar for both species and encompasses disruption of the plasma membrane and subsequently leakage of intracellular nucleotides leading to cell dead.
Starting Page	949
Ending Page	956
Page Count	8
File Format	PDF
ISSN	09660844
Journal	BioMetals
Volume Number	27
Issue Number	5
e-ISSN	15728773
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-06-25
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Burkholderia pseudomallei Burkholderia thailandensis Antimicrobial peptide LFchimera Lactoferrin Biochemistry Pharmacology/Toxicology Microbiology Cell Biology Plant Physiology Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences

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