Abstract
Leptospira spp. are pathogenic spirochetes that cause the zoonotic disease leptospirosis. Leptospiral immunoglobulin (Ig)-like protein B (LigB) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin, fibrinogen, laminin, elastin, tropoelastin and collagen. A high-affinity Fn-binding region of LigB has been localized to LigBCen2, which contains the partial 11th and full 12th Ig-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, the gelatin binding domain of fibronectin was shown to interact with LigBCen2R (KD = 1.91±0.40 µM). Not only LigBCen2R but also other Ig-like domains of Lig proteins including LigAVar7'-8, LigAVar10, LigAVar11, LigAVar12, LigAVar13, LigBCen7'-8, and LigBCen9 bind to GBD. Interestingly, a large gain in affinity was achieved through an avidity effect, with the terminal domains, 13th (LigA) or 12th (LigB) Ig-like repeat of Lig protein (LigAVar7'-13 and LigBCen7'-12) enhancing binding affinity approximately 51 and 28 fold, respectively, compared to recombinant proteins without this terminal repeat. In addition, the inhibited effect on MDCKs cells can also be promoted by Lig proteins with terminal domains, but these two domains are not required for gelatin binding domain binding and cell adhesion. Interestingly, Lig proteins with the terminal domains could form compact structures with a round shape mediated by multidomain interaction. This is the first report about the interaction of gelatin binding domain of Fn and Lig proteins and provides an example of Lig-gelatin binding domain binding mediating bacterial-host interaction.
Highlights
Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are a group of proteins located on the surface of microbes [1]
gelatin-binding domain (GBD) binds to LigBCen2R In order to fine map the GBD binding site of LigBCen2, LigBCen2 was truncated into LigBCen2R and LigBCen2NR [13]
isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) were applied to measure the binding of LigBCen2R to GBD
Summary
Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are a group of proteins located on the surface of microbes [1]. They are able to contribute to microbial adhesion by binding to extracellular matrixes (ECMs) of host cells and initiate infection [1]. Fn plays a pivotal role in bacterial-host interaction by interacting with MSCRAMMs [4] These MSCRAMMs may bind to NTD, GBD [5,6,7] or heparin-binding domain II [8,9]. Lig proteins, including LigA, LigB and LigC, contain 13, 12, and 13 Ig-like domains, respectively [25,26,27]. The N-terminal 630 amino acid residues of LigA and LigB are highly conserve, but the C-termini are variable [25,26,27]
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