title: Leptospira interrogans endostatin-like outer membrane proteins bind host fibronectin, laminin and regulators of complement.
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.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America. brian.stevenson@uky.edu
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
authors.forename: Henry A
authors.initials: HA
authors.lastname: Choy
authors.forename: Marija
authors.initials: M
authors.lastname: Pinne
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Rotondi
authors.forename: M Clarke
authors.initials: MC
authors.lastname: Miller
authors.forename: Edward
authors.initials: E
authors.lastname: Demoll
authors.forename: Peter
authors.initials: P
authors.lastname: Kraiczy
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cooley
authors.forename: Trevor P
authors.initials: TP
authors.lastname: Creamer
authors.forename: Marc A
authors.initials: MA
authors.lastname: Suchard
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brissette
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Verma
authors.forename: David A
authors.initials: DA
authors.lastname: Haake
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D003165:Complement System Proteins / Q000378:metabolism*; D017931:DNA Primers; D043169:Endostatins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism*; D005798:Genes, Bacterial; D007797:Laminin / Q000378:metabolism*; D007921:Leptospira interrogans / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D043169:Endostatins; D005353:Fibronectins; D007797:Laminin; D003165:Complement System Proteins