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Front Cell Infect Microbiol. 2017 May 9;7:163. doi: 10.3389/fcimb.2017.00163. eCollection 2017.

Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells.

Author information

1
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell UniversityIthaca, NY, USA.
2
National Research Center for Wildlife Borne Diseases, Institute of Zoology, Chinese Academy of SciencesBeijing, China.
3
Department of Veterinary Medicine, National Chung Hsing UniversityTaichung, Taiwan.
4
Research Center for Biotechnology, Xinxiang UniversityXinxiang, China.

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.

KEYWORDS:

Leptospira; LigB; extracellular matrix proteins; outer surface protein; protein-protein interaction; tropoelastin

PMID:
28536676
PMCID:
PMC5422739
DOI:
10.3389/fcimb.2017.00163
[Indexed for MEDLINE]
Free PMC Article

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