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Title: Phenol-Soluble Modulins From Staphylococcus aureus Biofilms Form Complexes With DNA to Drive Autoimmunity
The bacterial amyloid curli, produced by Enterobacteriales including Salmonella species and Escherichia coli , is implicated in the pathogenesis of several complex autoimmune diseases. Curli binds to extracellular DNA, and these complexes drive autoimmunity via production of anti-double-stranded DNA autoantibodies. Here, we investigated immune activation by phenol-soluble modulins (PSMs), the amyloid proteins expressed by Staphylococcus species. We confirmed the amyloid nature of PSMs expressed by S. aureus using a novel specific amyloid stain, ( E , E) -1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy) styrylbenzene (FSB). Direct interaction of one of the S. aureus PSMs, PSMα3, with oligonucleotides promotes fibrillization of PSM amyloids and complex formation with bacterial DNA. Finally, utilizing a mouse model with an implanted mesh-associated S. aureus biofilm, we demonstrated that exposure to S. aureus biofilms for six weeks caused anti-double-stranded DNA autoantibody production in a PSM-dependent manner. Taken together, these results highlight how the presence of PSM-DNA complexes in S. aureus biofilms can induce autoimmune responses, and suggest an explanation for how bacterial infections trigger autoimmunity.  more » « less
Award ID(s):
1808459
PAR ID:
10422613
Author(s) / Creator(s):
; ; ; ; ; ;
Date Published:
Journal Name:
Frontiers in Cellular and Infection Microbiology
Volume:
12
ISSN:
2235-2988
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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