biostudies-literatureChaurasia RNational Institute of Allergy and Infectious DiseasesNIAID NIH HHS859680https://www.ebi.ac.uk/biostudies/studies/S-EPMC9002632biostudies-literatureUnknown13Leptospirosis is a globally important neglected zoonotic disease. Previous data suggest that a family of virulence-modifying (VM) proteins (PF07598) is a distinctive feature of group I pathogenic <i>Leptospira</i> that evolved as important virulence determinants. Here, we show that one such VM protein, LA3490 (also known as Q8F0K3), is expressed by <i>Leptospira interrogans</i> serovar Lai, as a secreted genotoxin that is potently cytotoxic to human cells. Structural homology searches using Phyre2 suggested that VM proteins are novel R-type lectins containing tandem N-terminal ricin B-chain-like β-trefoil domains. Recombinant LA3490 (rLA3490) and an N-terminal fragment, t3490, containing only the predicted ricin B domain, bound to the terminal galactose and N-acetyl-galactosamine residues,Frontiers in microbiologyPathogenic <i>Leptospira</i> Evolved a Unique Gene Family Comprised of Ricin B-Like Lectin Domain-Containing Cytotoxins.PMC9002632R01 AI108276U19 AI115658R21 AI115273R21 AI164106Matthias MAMarroquin ASVinetz JMChaurasia RfalsePathogenic <i>Leptospira</i> Evolved a Unique Gene Family Comprised of Ricin B-Like Lectin Domain-Containing Cytotoxins.Leptospirosis is a globally important neglected zoonotic disease. Previous data suggest that a family of virulence-modifying (VM) proteins (PF07598) is a distinctive feature of group I pathogenic <i>Leptospira</i> that evolved as important virulence determinants. Here, we show that one such VM protein, LA3490 (also known as Q8F0K3), is expressed by <i>Leptospira interrogans</i> serovar Lai, as a secreted genotoxin that is potently cytotoxic to human cells. Structural homology searches using Phyre2 suggested that VM proteins are novel R-type lectins containing tandem N-terminal ricin B-chain-like β-trefoil domains. Recombinant LA3490 (rLA3490) and an N-terminal fragment, t3490, containing only the predicted ricin B domain, bound to the terminal galactose and N-acetyl-galactosamine residues,2022-01-01T00:00:00Z20222026-07-14T14:41:55.296Z2024-11-20T17:18:51.95ZS-EPMC90026323542277910.3389/fmicb.2022.859680