Abstract
The pathogenic spirochete Leptospira interrogans disseminates throughout its hosts via the bloodstream, then invades and colonizes a variety of host tissues. Infectious leptospires are resistant to killing by their hosts' alternative pathway of complement-mediated killing, and interact with various host extracellular matrix (ECM) components. The LenA outer surface protein (formerly called LfhA and Lsa24) was previously shown to bind the host ECM component laminin and the complement regulators factor H and factor H-related protein-1. We now demonstrate that infectious L. interrogans contain five additional paralogs of lenA, which we designated lenB, lenC, lenD, lenE and lenF. All six genes encode domains predicted to bear structural and functional similarities with mammalian endostatins. Sequence analyses of genes from seven infectious L. interrogans serovars indicated development of sequence diversity through recombination and intragenic duplication. LenB was found to bind human factor H, and all of the newly-described Len proteins bound laminin. In addition, LenB, LenC, LenD, LenE and LenF all exhibited affinities for fibronectin, a distinct host extracellular matrix protein. These characteristics suggest that Len proteins together facilitate invasion and colonization of host tissues, and protect against host immune responses during mammalian infection.
Highlights
Leptospirosis is a zoonotic disease of humans caused by the spirochete Leptospira interrogans and several other members of that genus [1]
In a previous study [12], members of our laboratories demonstrated that the lenA genes of serovar Pomona strain JEN4 and serovar Lai strain 56601 encode a factor H/factor H-related protein 1 (FHR-1) binding protein
Sequence analyses of additional L. interrogans strains from five other serovars indicated that all contain lenA loci
Summary
Leptospirosis is a zoonotic disease of humans caused by the spirochete Leptospira interrogans and several other members of that genus [1]. The prevalence of leptospirosis in many parts of the world is due to chronic kidney infection of a wide variety of domestic, peridomestic and wild reservoir host mammals, including rodents, pigs, cattle, horses and dogs. Colonization of the renal tubules of carrier animals results in shedding of virulent leptospires in the urine. Leptospires persist in fresh water until infection of a new host occurs via the conjunctiva, breaks in the skin or by invasion of mucous membranes in the respiratory or digestive tract. Infectious Leptospira spp. are endemic in many tropical and temperate areas of the world, presenting health threats to inhabitants of both rural and urban areas, as well as military personnel, aid workers, and tourists
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