Leptospira interrogans endostatin-like outer membrane proteins bind host fibronectin, laminin and regulators of complement.
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.
Stevenson
Brian
B
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America. brian.stevenson@uky.edu
Choy
Henry A
HA
Pinne
Marija
M
Rotondi
Matthew L
ML
Miller
M Clarke
MC
Demoll
Edward
E
Kraiczy
Peter
P
Cooley
Anne E
AE
Creamer
Trevor P
TP
Suchard
Marc A
MA
Brissette
Catherine A
CA
Verma
Ashutosh
A
Haake
David A
DA
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
D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D043169:Endostatins; D005353:Fibronectins; D007797:Laminin; D003165:Complement System Proteins