A Review on Host-Leptospira Interactions: What We Know and Future Expectations

Abstract

Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is considered a neglected infectious disease of human and veterinary concern. Our group has been investigating proteins annotated as hypothetical, predicted to be located on the leptospiral surface. Because of their location, these proteins may have the ability to interact with various host components, which could allow establishment of the infection. These proteins act as adherence factors by binding to host receptor molecules, such as the extracellular matrix (ECM) components laminin and glycosaminoglycans to help bacterial colonization. Leptospira also interacts with the host fibrinolytic system, which has been demonstrated to be a powerful tool for invasion mechanisms. The interaction with fibrinogen and thrombin has been shown to reduce fibrin clot formation. Additionally, the degradation of coagulation cascade components by secreted proteases or by acquired surface plasmin could also play a role in reducing clot formation, hence facilitating dissemination during infection. Interaction with host complement system regulators also plays a role in helping bacteria to evade the immune system, facilitating invasion. Interaction of Leptospira to cell receptors, such as cadherins, can contribute to investigate molecules that participate in virulence. To achieve a better understanding of the host-pathogen interaction, leptospiral mutagenesis tools have been developed and explored. This work presents several proteins that mediate binding to components of the ECM, plasma, components of the complement system and cells, to gather research achievements that can be helpful in better understanding the mechanisms of leptospiral-host interactions and discuss genetic manipulation for Leptospira spp. aimed at protein function validation.

Host Cell Binding Mediated by Leptospira interrogans Adhesins

“…Although many studies have shown that leptospires are able to bind to mammalian cells in vitro [ 4 ], this is the first study to investigate leptospires binding to mammalian cells using multiple different cell lines. We determined the adhesion profile of virulent, culture-attenuated and saprophytic strains of leptospires in EA.hy926, HMEC-1 and HULEC5a endothelial cells, in HEK293T and MDBK epithelial cells, and in E. Derm and BHK-21 fibroblasts.…”

“…Here, we investigated if the virulent, attenuated, and saprophytic strains of Leptospira and their major outer membrane proteins could bind to different mammalian cells, including endothelial and epithelial cells and fibroblasts. The first studies of leptospires adhesion to mammalian cells showed that virulent strains are more effective in binding to cells than are attenuated and saprophytic bacteria [ 4 ]. It was demonstrated that strains of L. interrogans serovars Canicola, Pomona, and Grippothyphosa interact with MDCK and PK-15 epithelial cells and HUVEC endothelial cells [ 17 ].…”

“…Studies of Borrelia and Leptospira have described several membrane proteins with redundant function. Those proteins are able to bind to various ECM components, such as collagen IV, cellular fibronectin, laminin, and/or plasma components, e.g., plasminogen and fibrinogen [ 3 , 4 , 5 ]. The number of molecules involved in these interactions suggests that both bacterial genera have a range of strategies to maintain infection.…”

Motility of the Zoonotic Spirochete Leptospira: Insight into Association with Pathogenicity

“…The severity of leptospirosis depends on the combination of the host species and the Leptospira serovars, but the link between the host-pathogen pairing and the outcome is ambiguous. Though it would be the consequence of a complicated host-pathogen interaction, such as an immunological attack and evasion [46], which might lead us to understand the mechanism from the Leptospira dynamics on the host tissues. The adhesivity and crawling-dependent spread investigated on kidney cells of various mammalian hosts show a positive correlation, and the typical maintenance host rat shows a lower score against pathogenic strains (i.e., low adhesivity and limited spread) [38].…”

Insight into the Structure, Functions, and Dynamics of the Leptospira Outer Membrane Proteins with the Pathogenicity

“…[ 13 , 14 ]. Besides these cell wall and cell membrane components, many virulence factors from the pathogenic Leptospira were identified and the structures and functions of this virulence were well studied in several reviews [ 15 , 16 , 17 ]. In addition, nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1 and NOD2) in the innate immune system are also very important pattern recognition receptors.…”