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[...]settings contain complex microbial and chemical compositions, facilitating a high rate of horizontal gene transfer that enables reworking of cellular functions to allow rapid adaptation to new environmental conditions and hosts. Virulent L. interrogans, but not the saprophytic Leptospira biflexa, disrupt adherens junctions of endothelial and epithelial cells in vitro, resulting in loss of VE- and E-cadherins and disruption of the associated catenins, which link cadherins to the intracellular actin cytoskeleton. A clue to the molecular mechanisms for endothelial barrier disruption emerged from a study examining the crystal structures of 4 L. interrogans leucine-rich repeat (LRR) proteins [20]. [...]C3H/HeJ mice lacking TLR4 are more susceptible to leptospiral infection have a higher leptospiral burden than C3H mice with an intact TLR4 [25].