FACIN, a Double-Edged Sword of the Emerging Periodontal Pathogen Filifactor alocis: A Metabolic Enzyme Moonlighting as a Complement Inhibitor.

Jusko, Monika; Miedziak, Beata; Ermert, David; Magda, Michal; King, Ben C; Bielecka, Ewa; Riesbeck, Kristian; Eick, Sigrun; Potempa, Jan; Blom, Anna M (2016). FACIN, a Double-Edged Sword of the Emerging Periodontal Pathogen Filifactor alocis: A Metabolic Enzyme Moonlighting as a Complement Inhibitor. Journal of immunology, 197(8), pp. 3245-3259. American Association of Immunologists 10.4049/jimmunol.1600739

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Periodontics Research

UniBE Contributor:

Eick, Sigrun

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

24 Apr 2017 15:32

Last Modified:

06 Oct 2017 13:50

Publisher DOI:

10.4049/jimmunol.1600739

PubMed ID:

27638863

BORIS DOI:

10.7892/boris.94801

URI:

https://boris.unibe.ch/id/eprint/94801

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