9hb2
Structure of the truncated version of IdeC protease C94S from Streptococcus canis
Structural highlights
FunctionPublication Abstract from PubMedStreptococcus canis is an important opportunistic pathogen of cats, dogs, and cows, which can cause a range of infections, ranging from skin and soft tissue infections to septicemia and endocarditis. As a zoonotic agent, S. canis has also recently been implicated in serious human infections, following trauma or immunosuppression. In this work, we describe a novel protease of S. canis, termed IdeC (Immunoglobulin G degrading enzyme of S. canis), which may be involved in bacterial immune evasion. The cleaving ability of IdeC against IgG from various species was assessed; this revealed that IdeC successfully cleaved canine, feline, and human IgG. We also confirmed that IdeC is a cysteine protease, similar to IdeS of Streptococcus pyogenes. Investigation of the cleavage site in IgG sequences showed that it is highly conserved across IgGs from all species tested. From this analysis, it was determined that IdeC cleavage occurs between the CH2 and hinge regions of IgG. Interestingly, feline IgG was consistently cleaved with the highest efficiency, with human and canine IgG displaying less efficient cleavage. High-resolution crystal structures of two IdeC constructs provided insights into the catalytic machinery and substrate recognition. Modeling of the full-length IdeC:IgG complexes for human, canine, and feline cases explains the mechanism of action of the protease and reveals the molecular basis for the observed cleavage preference for feline IgG. Understanding and managing S. canis as a pathogen is important in both veterinary and human medicine, as this bacterium underscores the need for awareness of zoonotic transmission. Structural and functional characterization of IdeC, a novel IgG-specific protease of Streptococcus canis.,Walsh S, Lapschies A-M, Miguel-Ruano V, Batuecas MT, Acebron-Avalos I, Kohler TP, Hammerschmidt S, Eichhorn I, Hermoso JA, Fulde M Infect Immun. 2025 Sep 9;93(9):e0024825. doi: 10.1128/iai.00248-25. Epub 2025 Jul , 31. PMID:40741973[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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