Abstract
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.
Highlights
Pathogenic species of Leptospira, a genus of the Gram-negative, spiral-shaped Spirochaeta family, are the causative agents of leptospirosis, a zoonotic infection that occurs globally
Single colonies were re-streaked to obtain clones for sequencing; only those that corresponded to the sequence of the L. interrogans genes were used for further experimentation
Each Maltose Binding Protein (MBP)-fusion protein was initially tested for the ability to bind to eight purified molecules that were previously shown to bind L. interrogans and that are components of the extracellular matrix
Summary
Pathogenic species of Leptospira, a genus of the Gram-negative, spiral-shaped Spirochaeta family, are the causative agents of leptospirosis, a zoonotic infection that occurs globally (reviewed in [1,2,3,4]). A majority of mammalian species have been shown to be potential carriers for Leptospira, including rodents, dogs, cats, cattle, pigs, and horses. Within these reservoir animals, the Leptospira colonize the kidneys ( the luminal aspect of the proximal tubule epithelium) without causing symptoms, while they slough off continually into the urine (reviewed in [1,2,3,4]). Human populations at risk for sporadic cases of leptospirosis include farmers, sewer workers, veterinarians, and slaughterhouse workers, but outbreaks of this disease are often associated with severe flooding events, in tropical regions [6,7,8]
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