title: FACIN, a Double-Edged Sword of the Emerging Periodontal Pathogen Filifactor alocis: A Metabolic Enzyme Moonlighting as a Complement Inhibitor.
abstract: Periodontal disease is one of the most common inflammatory infectious diseases worldwide and it is associated with other syndromes, such as cardiovascular disease or rheumatoid arthritis. Recent advances in sequencing allowed for identification of novel periodontopathogens such as Gram-positive Filifactor alocis, but its virulence mechanisms remain largely unknown. We confirmed that F. alocis is a prevalent species in periodontitis patients, and we also observed strong correlation of this bacterium with clinical parameters, highlighting its role in the pathogenesis of the disease. Further, we found that preincubation of human serum with F. alocis resulted in abolished bactericidal activity and that F. alocis was surviving readily in full blood. We demonstrated that one of the key contributors to F. alocis complement resistance is a unique protein, FACIN (F. alocis complement inhibitor), which binds to C3, resulting in suppression of all complement pathways. Interestingly, FACIN is a nonclassical cell surface protein, a cytosolic enzyme acetylornithine transaminase, for which we now identified a moonlighting function. FACIN binds to C3 alone, but more importantly it also captures activated complement factor 3 within the complex with factor B, thereby locking in the convertase in an inactive state. Because of the indispensable role of alternative pathway convertase in amplifying complement cascades, its inhibition by FACIN results in a very potent downregulation of activated complement factor 3 opsonization on the pathogen surface, accompanied by reduction of downstream C5 cleavage.
authors.affiliation: Section of Protein Chemistry, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Jusko
authors.affiliation: Section of Protein Chemistry, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden.
authors.forename: Beata
authors.initials: B
authors.lastname: Miedziak
authors.affiliation: Section of Protein Chemistry, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden.
authors.forename: David
authors.identifier: 0000-0003-4600-9070
authors.initials: D
authors.lastname: Ermert
authors.affiliation: Section of Protein Chemistry, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden.
authors.forename: Michal
authors.initials: M
authors.lastname: Magda
authors.affiliation: Section of Protein Chemistry, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden.
authors.forename: Ben C
authors.identifier: 0000-0001-6776-8741
authors.initials: BC
authors.lastname: King
authors.affiliation: Section of Protein Chemistry, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden.|Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.
authors.forename: Ewa
authors.identifier: 0000-0002-2631-6711
authors.initials: E
authors.lastname: Bielecka
authors.affiliation: Section of Clinical Microbiology, Department of Translational Medicine, Lund University, 202 13 Malmö, Sweden.
authors.forename: Kristian
authors.identifier: 0000-0001-6274-6965
authors.initials: K
authors.lastname: Riesbeck
authors.affiliation: Laboratory of Oral Microbiology, Department of Periodontology, University of Bern, 3010 Bern, Switzerland; and.
authors.forename: Sigrun
authors.identifier: 0000-0002-4619-2461
authors.initials: S
authors.lastname: Eick
authors.affiliation: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.|Centre for Oral Health and Systemic Diseases, University of Louisville School of Dentistry, Louisville, KY 40202.
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.affiliation: Section of Protein Chemistry, Department of Translational Medicine, Lund University, 205 02 Malmö, Sweden; anna.blom@med.lu.se.
authors.forename: Anna M
authors.identifier: 0000-0002-1348-1734
authors.initials: AM
authors.lastname: Blom
mesh_terms: D001421:Bacteria, Anaerobic / Q000201:enzymology* / Q000276:immunology*; D003167:Complement Activation; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D000637:Transaminases / Q000378:metabolism*
chemical_list: D003176:Complement C3; D000637:Transaminases