Abstract
Leptospira immunoglobulin-like protein B (LigB), a surface adhesin, is capable of mediating the attachment of pathogenic leptospira to the host through interaction with various components of the extracellular matrix (ECM). Human tropoelastin (HTE), the building block of elastin, confers resilience and elasticity to lung, and other tissues. Previously identified Ig-like domains of LigB, including LigB4 and LigB12, bind to HTE, which is likely to promote Leptospira adhesion to lung tissue. However, the molecular mechanism that mediates the LigB-HTE interaction is unclear. In this study, the LigB-binding site on HTE was further pinpointed to a N-terminal region of the 20th exon of HTE (HTE20N). Alanine mutants of basic and aromatic residues on HTE20N significantly reduced binding to the LigB. Additionally, HTE-binding site was narrowed down to the first β-sheet of LigB12. On this binding surface, residues F1054, D1061, A1065, and D1066 were critical for the association with HTE. Most importantly, the recombinant HTE truncates could diminish the binding of LigB to human lung fibroblasts (WI-38) by 68%, and could block the association of LigA-expressing L. biflexa to lung cells by 61%. These findings should expand our understanding of leptospiral pathogenesis, particularly in pulmonary manifestations of leptospirosis.
Highlights
Leptospirosis, a neglected yet serious infectious disease caused by pathogenic Leptospira, is considered the most widespread zoonosis in the world
Our group had identified that LigB Ig-like domains bound to 17th to 27th exon of human tropoelastin (HTE1727)
A wide variety of pathogenic bacteria, such as Staphylococcus (SchwarzLinek et al, 2004a,b; Vazquez et al, 2011), Mycobacteria (Kuo et al, 2012), Borrelia (Coburn et al, 2013), and Leptospira (Lin and Chang, 2007; Lin et al, 2009, 2010) have developed several different kinds of surface adhesins to attach to the host cells by interacting extracellular matrix (ECM) molecules including fibronectin, collagen, and elastin
Summary
Leptospirosis, a neglected yet serious infectious disease caused by pathogenic Leptospira, is considered the most widespread zoonosis in the world. A large number of leptospiral MSCRAMMs have been identified and thought to play multiple roles in binding to host ECM (Lin and Chang, 2007; Stevenson et al, 2007; Lin et al, 2009, 2010; Pinne et al, 2010). Among those MSCRAMMs, the Leptospira immunoglobulin-like (Lig) protein family is exclusively presented on the outer membrane of pathogenic Leptospira. Expressing Lig proteins on the surface of L. biflexa allowed the non-pathogenic spirochetes to gain the ability to bind to ECM molecules and to associate with mammalian cells (Figueira et al, 2011), which suggests Lig proteins are important for bacteria-host interactions
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