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A complex of equine lysozyme and oleic acid with bactericidal activity against Streptococcus pneumoniae

Clementi, Emily A; Wilhelm, Kristina R; Schleucher, Jürgen; Morozova-Roche, Ludmilla A and Hakansson, Anders P LU (2013) In PLoS ONE 8(11). p.80649-80649
Abstract

HAMLET and ELOA are complexes consisting of oleic acid and two homologous, yet functionally different, proteins with cytotoxic activities against mammalian cells, with HAMLET showing higher tumor cells specificity, possibly due to the difference in propensity for oleic acid binding, as HAMLET binds 5-8 oleic acid molecules per protein molecule and ELOA binds 11-48 oleic acids. HAMLET has been shown to possess bactericidal activity against a number of bacterial species, particularly those with a respiratory tropism, with Streptococcus pneumoniae displaying the greatest degree of sensitivity. We show here that ELOA also displays bactericidal activity against pneumococci, which at lower concentrations shows mechanistic similarities to... (More)

HAMLET and ELOA are complexes consisting of oleic acid and two homologous, yet functionally different, proteins with cytotoxic activities against mammalian cells, with HAMLET showing higher tumor cells specificity, possibly due to the difference in propensity for oleic acid binding, as HAMLET binds 5-8 oleic acid molecules per protein molecule and ELOA binds 11-48 oleic acids. HAMLET has been shown to possess bactericidal activity against a number of bacterial species, particularly those with a respiratory tropism, with Streptococcus pneumoniae displaying the greatest degree of sensitivity. We show here that ELOA also displays bactericidal activity against pneumococci, which at lower concentrations shows mechanistic similarities to HAMLET's bactericidal activity. ELOA binds to S. pneumoniae and causes perturbations of the plasma membrane, including depolarization and subsequent rupture, and activates an influx of calcium into the cells. Selective inhibition of calcium channels and sodium/calcium exchange activity significantly diminished ELOA's bactericidal activity, similar to what we have observed with HAMLET. Finally, ELOA-induced death was also accompanied by DNA fragmentation into high molecular weight fragments - an apoptosis-like morphological phenotype that is seen during HAMLET-induced death. Thus, in contrast to different mechanisms of eukaryote cell death induced by ELOA and HAMLET, these complexes are characterized by rather similar activities towards bacteria. Although the majority of these events could be mimicked using oleic acid alone, the concentrations of oleic acid required were significantly higher than those present in the ELOA complex, and for some assays, the results were not identical between oleic acid alone and the ELOA complex. This indicates that the lipid, as a common denominator in both complexes, is an important component for the complexes' bactericidal activities, while the proteins are required both to solubilize and/or present the lipid at the bacterial membrane and likely to confer other and separate functions during the bacterial death.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Biological Transport, Calcium, Cell Membrane, DNA Fragmentation, Dose-Response Relationship, Drug, Horses, Ions, Muramidase, Oleic Acid, Sodium-Calcium Exchanger, Streptococcus pneumoniae
in
PLoS ONE
volume
8
issue
11
pages
80649 - 80649
publisher
Public Library of Science
external identifiers
  • scopus:84894050234
ISSN
1932-6203
DOI
10.1371/journal.pone.0080649
language
English
LU publication?
no
id
b2c2bee8-3914-4002-af35-260c50d5e744
date added to LUP
2016-05-21 10:48:32
date last changed
2017-02-12 04:33:14
@article{b2c2bee8-3914-4002-af35-260c50d5e744,
  abstract     = {<p>HAMLET and ELOA are complexes consisting of oleic acid and two homologous, yet functionally different, proteins with cytotoxic activities against mammalian cells, with HAMLET showing higher tumor cells specificity, possibly due to the difference in propensity for oleic acid binding, as HAMLET binds 5-8 oleic acid molecules per protein molecule and ELOA binds 11-48 oleic acids. HAMLET has been shown to possess bactericidal activity against a number of bacterial species, particularly those with a respiratory tropism, with Streptococcus pneumoniae displaying the greatest degree of sensitivity. We show here that ELOA also displays bactericidal activity against pneumococci, which at lower concentrations shows mechanistic similarities to HAMLET's bactericidal activity. ELOA binds to S. pneumoniae and causes perturbations of the plasma membrane, including depolarization and subsequent rupture, and activates an influx of calcium into the cells. Selective inhibition of calcium channels and sodium/calcium exchange activity significantly diminished ELOA's bactericidal activity, similar to what we have observed with HAMLET. Finally, ELOA-induced death was also accompanied by DNA fragmentation into high molecular weight fragments - an apoptosis-like morphological phenotype that is seen during HAMLET-induced death. Thus, in contrast to different mechanisms of eukaryote cell death induced by ELOA and HAMLET, these complexes are characterized by rather similar activities towards bacteria. Although the majority of these events could be mimicked using oleic acid alone, the concentrations of oleic acid required were significantly higher than those present in the ELOA complex, and for some assays, the results were not identical between oleic acid alone and the ELOA complex. This indicates that the lipid, as a common denominator in both complexes, is an important component for the complexes' bactericidal activities, while the proteins are required both to solubilize and/or present the lipid at the bacterial membrane and likely to confer other and separate functions during the bacterial death.</p>},
  author       = {Clementi, Emily A and Wilhelm, Kristina R and Schleucher, Jürgen and Morozova-Roche, Ludmilla A and Hakansson, Anders P},
  issn         = {1932-6203},
  keyword      = {Animals,Biological Transport,Calcium,Cell Membrane,DNA Fragmentation,Dose-Response Relationship, Drug,Horses,Ions,Muramidase,Oleic Acid,Sodium-Calcium Exchanger,Streptococcus pneumoniae},
  language     = {eng},
  number       = {11},
  pages        = {80649--80649},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {A complex of equine lysozyme and oleic acid with bactericidal activity against Streptococcus pneumoniae},
  url          = {http://dx.doi.org/10.1371/journal.pone.0080649},
  volume       = {8},
  year         = {2013},
}