AUTHOR=Grando Kaitlyn , Nicastro Lauren K. , Tursi Sarah A. , De Anda Jaime , Lee Ernest Y. , Wong Gerard C. L. , Tükel Çağla 

TITLE=Phenol-Soluble Modulins From Staphylococcus aureus Biofilms Form Complexes With DNA to Drive Autoimmunity

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.884065

DOI=10.3389/fcimb.2022.884065

ISSN=2235-2988

ABSTRACT=<p>The bacterial amyloid curli, produced by Enterobacteriales including <italic>Salmonella</italic> species and <italic>Escherichia coli</italic>, is implicated in the pathogenesis of several complex autoimmune diseases. Curli binds to extracellular DNA, and these complexes drive autoimmunity <italic>via</italic> production of anti-double-stranded DNA autoantibodies. Here, we investigated immune activation by phenol-soluble modulins (PSMs), the amyloid proteins expressed by <italic>Staphylococcus</italic> species. We confirmed the amyloid nature of PSMs expressed by <italic>S. aureus</italic> using a novel specific amyloid stain, (<italic>E</italic>,<italic>E)</italic>-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy) styrylbenzene (FSB). Direct interaction of one of the <italic>S. aureus</italic> 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 <italic>S. aureus</italic> biofilm, we demonstrated that exposure to <italic>S. aureus</italic> 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 <italic>S. aureus</italic> biofilms can induce autoimmune responses, and suggest an explanation for how bacterial infections trigger autoimmunity.</p>