ArticleMicrobiology spectrum2025
Development of leptospiral virulence-modifying protein detection assay: implications for pathogenesis and diagnostic test development.
Article in Microbiology spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Leptospirosis, a globally significant neglected tropical disease, continues to lack early and reliable diagnostic methods despite over a century since the discovery of the disease and its etiological agent. Previously, we identified the pathogen-specific paralogous PF07598 gene family encoding virulence-modifying (VM) exotoxins, which play a critical role in leptospirosis pathogenesis. In this study, we developed a monoclonal antibody (mAb)-based capture immunoassay that detects VM proteins in the blood of experimental hamster models, validating the hypothesis that VM proteins function as secretory exotoxins that mediate disease pathogenesis. Monoclonal antibodies were generated against a natural variant, LA0591, a VM protein containing a conserved C-terminal DNase toxin domain but lacking N-terminal ricin B-like lectin domains. Epitope mapping identified specific linear epitopes targeted by mAbs 5F8, 5G10, and 6A5, with distinct binding regions confirmed through binning and peptide mapping. These mAbs demonstrated high-affinity binding to homologous antigens, with sub-picomolar dissociation constants (K IMPORTANCE: This research addresses the global health issue of leptospirosis, a neglected tropical disease that still lacks early and reliable diagnostic methods despite being known for over a century. The study has developed a novel test using specially designed antibodies to detect specific proteins related to the disease in the blood of infected hamsters. These proteins are linked to the pathogen's ability to cause illness. The successful detection of these proteins in the bloodstream is a significant advancement, as it not only improves our understanding of the disease's progression but also lays the groundwork for developing new diagnostic tools. This could lead to earlier and more accurate diagnoses of leptospirosis, potentially saving lives and reducing the impact of the disease globally.
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