Advancing serologic diagnosis: assessing the efficacy of rErpY-like protein in human leptospirosis detection

Cardoso, Thayná Laner; de Freitas, Stella Buchhorn; Seixas Neto, Amilton Clair Pinto; Balassiano, Ilana Teruszkin; Hartwig, Daiane Drawanz

doi:10.1007/s42770-024-01364-4

Braz J Microbiol

2024

DOI: 10.1007/s42770-024-01364-4

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Advancing serologic diagnosis: assessing the efficacy of rErpY-like protein in human leptospirosis detection

Thayná Laner Cardoso,

Stella Buchhorn de Freitas,

Amilton Clair Pinto Seixas Neto

et al.

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Cited by 2 publications

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ErpY-like Protein Interaction with Host Thrombin and Fibrinogen Intervenes the Plasma Coagulation through Extrinsic and Intrinsic Pathways

Hota,

Kumar

2024

ACS Infect. Dis.

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The survival and proliferation of pathogenic Leptospira within a host are complex phenomena that require careful consideration. The ErpYlike lipoprotein, found on the outer membrane surface of Leptospira, plays a crucial role in enhancing the bacterium's pathogenicity. The rErpY-like protein, in its recombinant form, contributes significantly to spirochete virulence by interacting with various host factors, including host complement regulators. This interaction facilitates the bacterium's evasion of the host complement system, thereby augmenting its overall pathogenicity. The rErpY-like protein exhibits a robust binding affinity to soluble fibrinogen, a vital component of the host coagulation system. In this study, we demonstrate that the rErpY-like protein intervenes in the clotting process of the platelet-poor citrated plasma of bovines and humans in a concentration-dependent manner. It significantly reduces clot density, alters the viscoelastic properties of the clot, and diminishes the average clotting rate in plasma. Furthermore, the ErpYlike protein inhibits thrombin-catalyzed fibrin formation in a dose-dependent manner and exhibits saturable binding to thrombin, suggesting its significant role in leptospiral infection. These findings provide compelling evidence for the anticoagulant effect of the ErpY-like lipoprotein and its significant role in leptospiral infection.

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ErpY-like Protein Interaction with Host Thrombin and Fibrinogen Intervenes the Plasma Coagulation through Extrinsic and Intrinsic Pathways

Hota,

Kumar

2024

ACS Infect. Dis.

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Unveiling the impact of Leptospira TolC efflux protein on host tissue adherence, complement evasion, and diagnostic potential

Hota,

Kumar

2024

Infect Immun

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The TolC family protein of Leptospira is a type I outer membrane efflux protein. Phylogenetic analysis revealed significant sequence conservation among pathogenic Leptospira species (83%–98% identity) compared with intermediate and saprophytic species. Structural modeling indicated a composition of six β-strands and 10 α-helices arranged in two repeats, resembling bacterial outer membrane efflux proteins. Recombinant TolC (rTolC), expressed in a heterologous host and purified via Ni-NTA chromatography, maintained its secondary structural integrity, as verified by circular dichroism spectroscopy. Polyclonal antibodies against rTolC detected native TolC expression in pathogenic Leptospira but not in nonpathogenic ones. Immunoassays and detergent fractionation assays indicated surface localization of TolC. The rTolC’s recognition by sera from leptospirosis-infected hosts across species suggests its utility as a diagnostic marker. Notably, rTolC demonstrated binding affinity for various extracellular matrix components, including collagen and chondroitin sulfate A, as well as plasma proteins such as factor H, C3b, and plasminogen, indicating potential roles in tissue adhesion and immune evasion. Functional assays demonstrated that rTolC-bound FH retained cofactor activity for C3b cleavage, highlighting TolC’s role in complement regulation. The rTolC protein inhibited both the alternative and the classical pathway-mediated membrane attack complex (MAC) deposition in vitro . Blocking surface-expressed TolC on leptospires using specific antibodies reduced FH acquisition by Leptospira and increased MAC deposition on the spirochete. These findings indicate that TolC contributes to leptospiral virulence by promoting host tissue colonization and evading the immune response, presenting it as a potential target for diagnostic and therapeutic strategies.

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Advancing serologic diagnosis: assessing the efficacy of rErpY-like protein in human leptospirosis detection

Cited by 2 publications

References 31 publications

ErpY-like Protein Interaction with Host Thrombin and Fibrinogen Intervenes the Plasma Coagulation through Extrinsic and Intrinsic Pathways

ErpY-like Protein Interaction with Host Thrombin and Fibrinogen Intervenes the Plasma Coagulation through Extrinsic and Intrinsic Pathways

Unveiling the impact of Leptospira TolC efflux protein on host tissue adherence, complement evasion, and diagnostic potential

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