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Title: A bipartite bacterial virulence factor targets the complement system and neutrophil activation

Journal Article · · The EMBO Journal (Online)

Abstract The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units. The N-terminal fragment has two immunoglobulin-like domains and binds with high affinity to the major neutrophil chemokine receptors FPR1 and CXCR1, blocking N -formyl-Met-Leu-Phe- and IL-8-induced neutrophil chemotaxis and activation. The C-terminal fragment functions as a cysteine protease with a unique proteolytic activity and structure, which degrades several components of the complement system, such as C3 and C3b. Murine infection studies further reveal a critical T-Mac role in tissue damage and inflammation caused by bacterial infection. Collectively, these results disclose a novel innate immunity-evasion strategy, and open avenues for investigating the role of cysteine proteases and immunoglobulin-like domains of gram-positive and -negative bacterial pathogens.

Sponsoring Organization:
USDOE
Grant/Contract Number:
SC0012704
OSTI ID:
2496312
Journal Information:
The EMBO Journal (Online), Journal Name: The EMBO Journal (Online) Journal Issue: 4 Vol. 44; ISSN 1460-2075
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United Kingdom
Language:
English

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