20.500.12556/DKUM-91689 Ribotype classification of Clostridioides difficile isolates Is not predictive of the amino acid sequence diversity of the toxin virulence factors TcdA and TcdB Clostridioides (Clostridium) difficile is the most commonly recognized cause of infectious diarrhea in healthcare settings. Currently there is no vaccine to prevent initial or recurrent C. difficile infection (CDI). Two large clostridial toxins, TcdA and TcdB, are the primary virulence factors for CDI. Immunological approaches to prevent CDI include antibody-mediated neutralization of the cytotoxicity of these toxins. An understanding of the sequence diversity of the two toxins expressed by disease causing isolates is critical for the interpretation of the immune response to the toxins. In this study, we determined the whole genome sequence (WGS) of 478 C. difficile isolates collected in 12 countries between 2004 and 2018 to probe toxin variant diversity. A total of 44 unique TcdA variants and 37 unique TcdB variants were identified. The amino acid sequence conservation among the TcdA variants (>98%) is considerably greater than among the TcdB variants (as low as 86.1%), suggesting that different selection pressures may have contributed to the evolution of the two toxins. Phylogenomic analysis of the WGS data demonstrate that isolates grouped together based on ribotype or MLST code for multiple different toxin variants. These findings illustrate the importance of determining not only the ribotype but also the toxin sequence when evaluating strain coverage using vaccine strategies that target these virulence factors. We recommend that toxin variant type and sequence type (ST), be used together with ribotype data to provide a more comprehensive strain classification scheme for C. difficile surveillance during vaccine development objectives. Clostridioides difficile Clostridium difficile TCDB TcdA vaccines whole genome sequencing Clostridioides difficile Clostridium difficile cepiva sekvenciranje genoma true false true Frontiers Research Foundation Angleški jezik Slovenski jezik Znanstveno delo 2025-01-28 12:11:14 2025-01-28 12:25:33 2025-01-29 03:12:03 0000-00-00 00:00:00 2020 0 0 Str. 1-13 št. članka 1310 Letn. 11 June 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2019-12-11 2020-05-25 2020-06-19 579.852.13 26304259 10.3389/fmicb.2020.01310 1664-302X Li-2020-Ribotype_Classification_of_i_Clostridi.pdf Li-2020-Ribotype_Classification_of_i_Clostridi.pdf 1 77647C50953C17B59D9B1DCDAE47CC1C f4bcadc95f755bf68bda32e702d569a7dd5d680997b9db49cd80e6970ef3d4f7 6c0ad1ad-dd6a-11ef-9187-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=188209 https://doi.org/10.3389/fmicb.2020.01310 0 9823d95e-dd68-11ef-9187-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=188207 Medicinska fakulteta 0 0 0