Apolipoprotein B Is an innate barrier against invasive Staphylococcus aureus infection.

Abstract

Staphylococcus aureus is both a colonizer of humans and a cause of severe invasive infections. Although the genetic basis for phenotype switching from colonizing to invasive has received significant study, knowledge of host factors that antagonize the switch is limited. We show that VLDL and LDL lipoproteins interfere with this switch by antagonizing the S. aureus agr quorum-sensing system that upregulates genes required for invasive infection. The mechanism of antagonism entails binding of the major structural protein of these lipoproteins, apolipoprotein B, to an S. aureus autoinducing pheromone, preventing attachment of this pheromone to the bacteria and subsequent signaling through its receptor, AgrC. Mice deficient in plasma apolipoprotein B, either genetically or pharmacologically, are more susceptible to invasive agr+ bacterial infection, but not to infection with an agr deletion mutant. Therefore, apolipoprotein B at homeostatic levels in blood is an essential innate defense effector against invasive S. aureus infection.

• Authors: M Michal Peterson, Jessica L Mack, Pamela R Hall, Anny A Alsup, Susan M Alexander, Erin K Sully, Youhanna S Sawires, Ambrose L Cheung, Michael Otto, Hattie D Gresham
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 4 Issue 6 Pg. 555-66 (Dec 11 2008) ISSN: 1934-6069 [Electronic] United States
• PMID: 19064256 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Agr protein, Staphylococcus aureus
• Apolipoproteins B
• Bacterial Proteins
• Pheromones
• Trans-Activators
• Protein Kinases
• AgrC protein, Staphylococcus

Topics

• Animals
• Apolipoproteins B (deficiency, immunology, metabolism)
• Bacterial Proteins (genetics, metabolism)
• Body Weight
• Carrier State (microbiology)
• Gene Deletion
• Humans
• Lung (microbiology)
• Mice
• Mice, Knockout
• Pheromones (metabolism)
• Protein Binding
• Protein Kinases (metabolism)
• Spleen (microbiology)
• Staphylococcal Infections (microbiology)
• Staphylococcus aureus (immunology)
• Survival Analysis
• Trans-Activators (genetics, metabolism)