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.