RESUMEN

Leptospirosis is a zoonosis caused by pathogenic Leptospira spp. In this study, we report that the recombinant proteins LIC10507, LIC10508 and LIC10509 are recognized by confirmed leptospirosis serum samples at both phases of the disease. The recombinant rLIC10508 and rLIC10507 are plasminogen (PLG)-binding proteins, capable of generating plasmin in the presence of a PLG activator. The proteins bind to PLG in a dose-dependent and saturable manner, fulfilling host–ligandinteraction. Furthermore, rLIC10508 interacts with fibrinogen (Fg), plasma fibronectin and C4b binding protein (C4BP). The binding of rLIC10508 to Fg decreases the fibrin clotting in a thrombin-catalyzed reaction. The incubation with 4 μMof protein promoted 40% inhibition upon clotting formation. C4BP bound to rLIC10508 retained its cofactor activity forfactor I promoting the cleavage of C4b protein, which may reduce the membrane attack complex formation. Although these proteins have high amino acid sequence similarity, rLIC10508 is the most talented of the three, a behavior that might be explained by its unique putative 3D structure, whereas structures of rLIC10507 and rLIC10509 are very similar. Plasmingeneration (rLIC10507 and rLIC10508), together with decreasing fibrin clot formation (rLIC10508) and impairment of the complement system (rLIC10508) may help the bacteria to overcome host defense, facilitating the infection process...

Asunto(s)

Humanos , Fibrinolisina/análisis , Leptospira/crecimiento & desarrollo , Leptospirosis/epidemiología , Leptospirosis/genética

RESUMEN

Leptospirosis is an acute febrile disease caused by pathogenic spirochetes of the genus Leptospira. It is considered an important re-emerging infectious disease that affects humans worldwide. The knowledge about the mechanisms by which pathogenic leptospires invadeand colonize the host remains limited since very few virulence factors contributing to the pathogenesis of the disease have been identified. Here, we report the identification and characterization of two new leptospiral proteins with OmpA-like domains. The recombinant proteins,which exhibit extracellular matrix-binding properties, are called Lsa46 - LIC13479 andLsa77 - LIC10050 (Leptospiral surface adhesins of 46 and 77 kDa, respectively). Attachmentof Lsa46 and Lsa77 to laminin was specific, dose dependent and saturable, with KD valuesof 24.3 ± 17.0 and 53.0 ± 17.5 nM, respectively. Lsa46 and Lsa77 also bind plasma fibronectin,and both adhesins are plasminogen (PLG)-interacting proteins, capable of generatingplasmin (PLA) and as such, increase the proteolytic ability of leptospires. The proteins corresponding to Lsa46 and Lsa77 are present in virulent L. interrogans L1-130 and in saprophyteL. biflexa Patoc 1 strains, as detected by immunofluorescence. The adhesins are recognizedby human leptospiros is serum samples at the on set and convalescent phases of the disease, suggesting that they are expressed during infection. Taken together, our data could offer valuable information to the understanding of leptospiral pathogenesis...

Asunto(s)

Animales , Leptospira/crecimiento & desarrollo , Leptospira/genética , Leptospirosis/diagnóstico , Leptospirosis/epidemiología , Leptospirosis/transmisión

RESUMEN

Proca's equations for two types of fields in a Dirac's aether with electric conductivity sigma are solved exactly. The Proca electromagnetic fields are assumed with cylindrical symmetry. The background is a static, curved spacetime whose spatial section is homogeneous and has the topology of either the three-sphere S 3 or the projective three-space P 3. Simple relations between the range of Proca field lambda, the Universe radius R, the limit of photon rest mass mgamma and the conductivity sigma are written down.