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Início
Agenda |
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- 11 de novembro de 2014
16h30
F-210 -
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Thereza A. Soares
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Departamento de
Química Fundamental - UFPE
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Computational
Simulations of Bacterial Outer Membranes
Lipopolysaccharides
(LPS) are the major constituent of bacterial outer membranes,
acting as an effective permeability barrier against xenobiotic
agents and the host cell defense system. LPS is also a potent
activator of the mammalian immune system in amounts as little as
fmol. Variable external conditions prompt structural and
chemical modifications of the bacterial outer membrane,
enhancing the organism ability to evade the host immune defence
and colonize specific tissues. Changes in temperature and/or
specific ion concentration have been shown to trigger lamellar
to non-lamellar transitions in LPS membranes. We have previously
developed and validated an atomistic model of the LPS membrane
of Pseudomonas aeruginosa, which has been used to investigate
its structural dynamics, hydration and electrostatic properties.
In this work, we have expanded our atomistic model to include
novel LPS chemotypes expressed by P. aeruginosa during outer
membrane remodeling. We have found that decrease in the LPS
polysaccharide chain length occurs with increase in the
diffusion coefficients for the Ca2+ counter-ions, increase in
acyl chain packing (decrease in membrane fluidity), and decrease
of the negative potential across the LPS surface. We have also
investigated the effect of mono- and divalent cations on the
stability of LPS and Lipid-A membranes. Our findings suggest
that the stability of LPS membranes reflects a balance between
effective membrane hydration, ionic valence and aptness to
cross-link neighbouring molecules. These findings reproduce
experimental trends while providing atom-level structural
information on the rough LPS chemotypes that can help to
rationalize antibiotic resistance and bacterial adhesion
processes.
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