Heterologous production of the adhesin LIC13411 from pathogenic Leptospira facilitates binding of non-pathogenic Leptospira in vitro and in vivo

Heterologous production of the adhesin LIC13411 from pathogenic Leptospira facilitates binding of non-pathogenic Leptospira in vitro and in vivo

Blog Article

Leptospirosis is an important cause of morbidity and mortality worldwide.Disease severity ranges from asymptomatic where can i buy walnettos candy colonization to widespread hemorrhage and multiorgan dysfunction.The causative agents, Leptospira spp.

, are zoonotic Gram-negative spirochetes.One important step in pathogenesis is binding of bacterial adhesins to host components.Previously our laboratory identified two L.

interrogans candidate adhesins, LIC11574 and LIC13411, that bind to VE-cadherin in vitro.In the current study, we demonstrate the ability of two strains of pathogenic L.interrogans to disrupt the localization of VE-cadherin, a protein important to maintaining inter-endothelial junctions.

Purified MBP-LIC11574 and MBP-LIC13411 bind human dermal microvascular endothelial cells in a pattern reminiscent of VE-cadherin, but do not disrupt VE-cadherin localization.Genes encoding the candidate adhesins from pathogenic Leptospira were cloned in an overexpression vector and introduced into non-pathogenic L.biflexa, creating gain-of-function strains producing LIC11574 or LIC13411.

Protein production and localization to the outer membrane were confirmed by Triton X-114 fractionation.Although these strains do not disrupt VE-cadherin localization, production of LIC13411 increases binding of non-pathogenic Leptospira to human endothelial cells and specifically to VE-cadherin.In a short-term murine model of infection, LIC13411 production led to increased burdens of the non-pathogen in the lung, liver, kidney, and bladder.

These data confirm the role of LIC13411 as an adhesin in Leptospira spp.and implicate it in dissemination to multiple organs.Importantly, anti-adhesin hp 27xq therapy has been shown to have many benefits over classical antibiotics.

Taken together, this work provides novel insight into the pathogenesis of Leptospira spp.and identifies LIC13411 as a potential prophylactic and therapeutic target.