Apolipoprotein B Is an innate barrier against invasive Staphylococcus aureus infection.
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.
Peterson
M Michal
MM
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Mack
Jessica L
JL
Hall
Pamela R
PR
Alsup
Anny A
AA
Alexander
Susan M
SM
Sully
Erin K
EK
Sawires
Youhanna S
YS
Cheung
Ambrose L
AL
Otto
Michael
M
Gresham
Hattie D
HD
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
C095698:Agr protein, Staphylococcus aureus; D001055:Apolipoproteins B; D001426:Bacterial Proteins; D010675:Pheromones; D015534:Trans-Activators; D011494:Protein Kinases; C531166:AgrC protein, Staphylococcus