title: 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.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
authors.forename: M Michal
authors.initials: MM
authors.lastname: Peterson
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mack
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Hall
authors.forename: Anny A
authors.initials: AA
authors.lastname: Alsup
authors.forename: Susan M
authors.initials: SM
authors.lastname: Alexander
authors.forename: Erin K
authors.initials: EK
authors.lastname: Sully
authors.forename: Youhanna S
authors.initials: YS
authors.lastname: Sawires
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.forename: Hattie D
authors.initials: HD
authors.lastname: Gresham
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001835:Body Weight; D002353:Carrier State / Q000382:microbiology; D017353:Gene Deletion; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D010675:Pheromones / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D016019:Survival Analysis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001055:Apolipoproteins B; D001426:Bacterial Proteins; D010675:Pheromones; D015534:Trans-Activators; D011494:Protein Kinases; C531166:AgrC protein, Staphylococcus