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Manterola, Lorea;
Moriyón, Ignacio;
Moreno, Edgardo;
Sola-Landa, Alberto;
Weiss, David S.;
Koch, Michel H. J.;
Howe, Jörg;
Brandenburg, Klaus;
López-Goñi, Ignacio
The Lipopolysaccharide of Brucella abortus BvrS/BvrR Mutants Contains Lipid A Modifications and Has Higher Affinity for Bactericidal Cationic Peptides
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- Medientyp: E-Artikel
- Titel: The Lipopolysaccharide of Brucella abortus BvrS/BvrR Mutants Contains Lipid A Modifications and Has Higher Affinity for Bactericidal Cationic Peptides
- Beteiligte: Manterola, Lorea; Moriyón, Ignacio; Moreno, Edgardo; Sola-Landa, Alberto; Weiss, David S.; Koch, Michel H. J.; Howe, Jörg; Brandenburg, Klaus; López-Goñi, Ignacio
- Erschienen: American Society for Microbiology, 2005
- Erschienen in: Journal of Bacteriology
- Umfang: 5631-5639
- Sprache: Englisch
- DOI: 10.1128/jb.187.16.5631-5639.2005
- ISSN: 0021-9193; 1098-5530
- Schlagwörter: Molecular Biology ; Microbiology
- Zusammenfassung: <jats:title>ABSTRACT</jats:title> <jats:p> The two-component BvrS/BvrR system is essential for <jats:italic>Brucella abortus</jats:italic> virulence. It was shown previously that its dysfunction abrogates expression of some major outer membrane proteins and increases bactericidal peptide sensitivity. Here, we report that BvrS/BvrR mutants have increased surface hydrophobicity and susceptibility to killing by nonimmune serum. The <jats:italic>bvrS</jats:italic> and <jats:italic>bvrR</jats:italic> mutant lipopolysaccharides (LPSs) bound more polymyxin B, chimeras constructed with <jats:italic>bvrS</jats:italic> mutant cells and parental LPS showed augmented polymyxin B resistance, and, conversely, parental cells and <jats:italic>bvrS</jats:italic> mutant LPS chimeras were more sensitive and displayed polymyxin B-characteristic outer membrane lesions, implicating LPS as being responsible for the phenotype of the BvrS/BvrR mutants. No qualitative or quantitative changes were detected in other envelope and outer membrane components examined: periplasmic β(1-2) glucans, native hapten polysaccharide, and phospholipids. The LPS of the mutants was similar to parental LPS in O-polysaccharide polymerization and fine structure but showed both increased underacylated lipid A species and higher acyl-chain fluidity that correlated with polymyxin B binding. These lipid A changes did not alter LPS cytokine induction, showing that in contrast to other gram-negative pathogens, recognition by innate immune receptors is not decreased by these changes in LPS structure. Transcription of <jats:italic>Brucella</jats:italic> genes required for incorporating long acyl chains into lipid A ( <jats:italic>acpXL</jats:italic> and <jats:italic>lpxXL</jats:italic> ) or implicated in lipid A acylation control ( <jats:italic>bacA</jats:italic> ) was not affected. We propose that in <jats:italic>Brucella</jats:italic> the outer membrane homeostasis depends on the functioning of BvrS/BvrR. Accordingly, disruption of BvrS/BvrR damages the outer membrane, thus contributing to the severe attenuation manifested by <jats:italic>bvrS</jats:italic> and <jats:italic>bvrR</jats:italic> mutants. </jats:p>
-
Beschreibung:
<jats:title>ABSTRACT</jats:title>
<jats:p>
The two-component BvrS/BvrR system is essential for
<jats:italic>Brucella abortus</jats:italic>
virulence. It was shown previously that its dysfunction abrogates expression of some major outer membrane proteins and increases bactericidal peptide sensitivity. Here, we report that BvrS/BvrR mutants have increased surface hydrophobicity and susceptibility to killing by nonimmune serum. The
<jats:italic>bvrS</jats:italic>
and
<jats:italic>bvrR</jats:italic>
mutant lipopolysaccharides (LPSs) bound more polymyxin B, chimeras constructed with
<jats:italic>bvrS</jats:italic>
mutant cells and parental LPS showed augmented polymyxin B resistance, and, conversely, parental cells and
<jats:italic>bvrS</jats:italic>
mutant LPS chimeras were more sensitive and displayed polymyxin B-characteristic outer membrane lesions, implicating LPS as being responsible for the phenotype of the BvrS/BvrR mutants. No qualitative or quantitative changes were detected in other envelope and outer membrane components examined: periplasmic β(1-2) glucans, native hapten polysaccharide, and phospholipids. The LPS of the mutants was similar to parental LPS in O-polysaccharide polymerization and fine structure but showed both increased underacylated lipid A species and higher acyl-chain fluidity that correlated with polymyxin B binding. These lipid A changes did not alter LPS cytokine induction, showing that in contrast to other gram-negative pathogens, recognition by innate immune receptors is not decreased by these changes in LPS structure. Transcription of
<jats:italic>Brucella</jats:italic>
genes required for incorporating long acyl chains into lipid A (
<jats:italic>acpXL</jats:italic>
and
<jats:italic>lpxXL</jats:italic>
) or implicated in lipid A acylation control (
<jats:italic>bacA</jats:italic>
) was not affected. We propose that in
<jats:italic>Brucella</jats:italic>
the outer membrane homeostasis depends on the functioning of BvrS/BvrR. Accordingly, disruption of BvrS/BvrR damages the outer membrane, thus contributing to the severe attenuation manifested by
<jats:italic>bvrS</jats:italic>
and
<jats:italic>bvrR</jats:italic>
mutants.
</jats:p> - Anmerkungen:
- Zugangsstatus: Freier Zugang