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Identification of cell-binding adhesins of Leptospira interrogans. PLoS Negl Trop Dis 2014 Oct;8(10):e3215 PMID: 25275630 PMCID: PMC4183468

Pubmed ID

25275630

DOI

10.1371/journal.pntd.0003215

Abstract

Leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus Leptospira. Infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. The adhesion of pathogenic Leptospira species (spp.), the causative agent of leptospirosis, to host tissue components is necessary for infection and pathogenesis. While it is well-established that extracellular matrix (ECM) components play a role in the interaction of the pathogen with host molecules, we have shown that pathogenic Leptospira interrogans binds to host cells more efficiently than to ECM components. Using in vitro phage display to select for phage clones that bind to EA.hy926 endothelial cells, we identified the putative lipoproteins LIC10508 and LIC13411, and the conserved hypothetical proteins LIC12341 and LIC11574, as candidate L. interrogans sv. Copenhageni st. Fiocruz L1-130 adhesins. Recombinant LIC11574, but not its L. biflexa homologue LBF1629, exhibited dose-dependent binding to both endothelial and epithelial cells. In addition, LIC11574 and LIC13411 bind to VE-cadherin, an endothelial cell receptor for L. interrogans. Extraction of bacteria with the non-ionic detergent Triton X-114 resulted in partitioning of the candidate adhesins to the detergent fraction, a likely indication that these proteins are outer membrane localized. All candidate adhesins were recognized by sera obtained from leptospirosis patients but not by sera from healthy individuals as assessed by western blot. This work has identified bacterial adhesins that are potentially involved in L. interrogans infection of the mammalian host, and through cadherin binding, may contribute to dissemination and vascular damage. Our findings may be of value in leptospirosis control and prevention, with the bacterial adhesins potentially serving as targets for development of diagnostics, therapeutics, and vaccines.

Author List

Evangelista KV, Hahn B, Wunder EA Jr, Ko AI, Haake DA, Coburn J

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84920527866   14 Citations

MESH terms used to index this publication - Major topics in bold

Adhesins, Bacterial
Animals
Bacterial Adhesion
Cadherins
Cells, Cultured
Endothelial Cells
Extracellular Matrix
Female
Humans
Leptospira interrogans
Leptospirosis
Lipoproteins
Mice
Mice, Inbred BALB C
Peptide Library
Recombinant Proteins
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70