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

• DOI: 10.3389/fcimb.2022.884065
• Publication Date: 2022-05-11T14:09:25Z
• Authors: Kaitlyn Grando; Lauren K. Nicastro; Sarah A. Tursi; Jaime De Anda; Ernest Y. Lee; Gerard C. L. Wong; Çağla Tükel
• Keywords: Amyloid (mycology); Pathogenesis

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, these complexes drive autoimmunity via production anti-double-stranded DNA autoantibodies. Here, we investigated immune activation phenol-soluble modulins (PSMs), proteins expressed Staphylococcus species. We confirmed nature PSMs S. aureus using a novel specific stain, ( E E) -1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy) styrylbenzene (FSB). Direct interaction one PSMs, PSMα3, with oligonucleotides promotes fibrillization PSM amyloids formation DNA. Finally, utilizing mouse model an implanted mesh-associated biofilm, demonstrated that exposure biofilms for six weeks caused autoantibody PSM-dependent manner. Taken together, results highlight how presence PSM-DNA can induce responses, suggest explanation infections trigger autoimmunity.