Project description:Isolation and characterization of two recently isolated Novosphingobium oxfordensis sp. nov. and Novosphingobium mississippiensis sp. nov. strains from soil, with LCMS and genome-based investigation of their glycosphingolipid productions
Project description:Clostridioides difficile infection (CDI), caused by strains producing toxin B (TcdB), poses a significant global health threat. While C. difficile exhibits substantial diversity, functional studies have focused on a limited number of isolates, overlooking other genomospecies within the genus. We describe five isolates from patients suspected of having CDI who tested negative for the PaLoc marker gene tcdC. Through genomic, proteomic, and phenotypic analyses, we demonstrate that they correspond to three novel toxin-producing species, designated as Clostridioides cryptodifficilis sp. nov., Clostridioides divergens sp. nov., and Clostridioides subdifficilis sp. nov. These species are distinguished by unique MALDI-ToF signatures, metabolic capabilities, and genomic and proteomic architectures, underscoring their clear taxonomic and functional divergence from C. difficile. They secrete functionally active TcdB7 or TcdB11, as demonstrated by cytotoxicity assays in cultured cells and in vivo using the mouse ileal loop model, implicating them in disease pathology, albeit with lower virulence than C. difficile. Our findings expand the known diversity of TcdB-producing Clostridioides and have direct implications for diagnostics, surveillance, and clinical management of diarrheal diseases.
Project description:Clostridioides difficile infection (CDI), caused by strains producing toxin B (TcdB), poses a significant global health threat. While C. difficile exhibits substantial diversity, functional studies have focused on a limited number of isolates, overlooking other genomospecies within the genus. We describe five isolates from patients suspected of having CDI who tested negative for the PaLoc marker gene tcdC. Through genomic, proteomic, and phenotypic analyses, we demonstrate that they correspond to three novel toxin-producing species, designated as Clostridioides cryptodifficilis sp. nov., Clostridioides divergens sp. nov., and Clostridioides subdifficilis sp. nov. These species are distinguished by unique MALDI-ToF signatures, metabolic capabilities, and genomic and proteomic architectures, underscoring their clear taxonomic and functional divergence from C. difficile. They secrete functionally active TcdB7 or TcdB11, as demonstrated by cytotoxicity assays in cultured cells and in vivo using the mouse ileal loop model, implicating them in disease pathology, albeit with lower virulence than C. difficile. Our findings expand the known diversity of TcdB-producing Clostridioides and have direct implications for diagnostics, surveillance, and clinical management of diarrheal diseases.
