Evaluation of cell binding activities of Leptospira ECM adhesins

Autor: Jenifer Coburn, Gregory T. Robbins, Beth L. Hahn, Karen V. Evangelista, Patrick S. Aranda, Lavinia J. Padmore
Rok vydání: 2015
Předmět:
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003712 (2015)
ISSN: 1935-2735
Popis: Pathogenic spirochetes of the genus Leptospira are the causative agents of leptospirosis, a zoonotic infection that occurs globally. The bacteria colonize the renal proximal tubules of many animals and are shed in the urine. Contact with the urine, or with water contaminated with the urine of infected animals can cause infection of new host animals, including humans. Mechanisms of colonization of the proximal tubule and other tissues are not known, but specific interactions between bacterial adhesins and host substrates are likely to be critical in this process. Several extracellular matrix (ECM) adhesins have been previously identified, but more recently, it has been shown that Leptospira bind more efficiently to cells than ECM. In this work, recombinant forms of five putative Leptospira ECM adhesins, namely LipL32, Loa22, OmpL1, p31/LipL45, and LenA were evaluated for binding to cells as well as an expanded variety of ECM components. Reproducible and significant adhesin activity was demonstrated only for OmpL1, which bound to both mammalian cell lines tested and to glycosaminoglycans (GAGs). While determination of biologically significant bacterial adhesion activity will require generation of site-directed mutant strains, our results suggest that OmpL1 is a strong candidate for future evaluation regarding the roles of the adhesin activity of the protein during L. interrogans infection.
Author Summary Leptospirosis is the most widespread zoonotic infection in the world and represents a major public health problem, especially in tropical climates. The processes by which some Leptospira species cause infection, disease, and colonization of carrier animals remains poorly understood. Specific binding of Leptospira molecules and host molecules are likely important for infection and colonization. To identify Leptospira molecules that mediate attachment to host substrates, prior studies have evaluated Leptospira membrane proteins for binding to extracellular matrix (ECM) proteins. More recent data, however, show that Leptospira bind more efficiently to cells than to ECM. In search of adhesins mediating the latter activity, our study evaluated the direct cell binding activity of recombinant forms of a group of previously reported Leptospira ECM adhesins. Only one of these proteins, OmpL1, demonstrated reproducible direct cell binding activity. Further work will focus on identification of the mammalian receptor for OmpL1 and determining the biological significance of this activity during infection.
Databáze: OpenAIRE
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