In vivo animal models confirm an increased virulence potential and pathogenicity of the NAP1/RT027/ST01 genotype within the Clostridium difficile MLST Clade 2.
In vivo animal models confirm an increased virulence potential and pathogenicity of the NAP1/RT027/ST01 genotype within the Clostridium difficile MLST Clade 2.
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DOI：
10.1186/s13099-020-00383-4
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发表时间：
2020
期刊：
影响因子：
4.2
通讯作者：
Quesada-Gómez C
中科院分区：
文献类型：
--
作者：
Orozco-Aguilar J;Alfaro-Alarcón A;Acuña-Amador L;Chaves-Olarte E;Rodríguez C;Quesada-Gómez C
Based on MLST analyses the global population of C. difficile is distributed in eight clades, of which Clade 2 includes the “hypervirulent” NAP1/RT027/ST01 strain along with various unexplored sequence types (STs). To clarify whether this clinically relevant phenotype is a widespread feature of C. difficile Clade 2, we used the murine ileal loop model to compare the in vivo pro-inflammatory (TNF-α, IL-1β, IL-6) and oxidative stress activities (MPO) of five Clade 2 clinical C. difficile isolates from sequence types (STs) 01, 41, 67, and 252. Besides, we infected Golden Syrian hamsters with spores from these strains to determine their lethality, and obtain a histological evaluation of tissue damage, WBC counts, and serum injury biomarkers (LDH, ALT, AST, albumin, BUN, creatinine, Na+, and Cl−). Genomic distances were calculated using Mash and FastANI to explore whether the responses were dictated by phylogeny. The ST01 isolate tested ranked first in all assays, as it induced the highest overall levels of pro-inflammatory cytokines, MPO activity, epithelial damage, biochemical markers, and mortality measured in both animal models. Statistically indistinguishable or rather similar outputs were obtained for a ST67 isolate in tests such as tissue damage, neutrophils count, and lethal activity. The results recorded for the two ST41 isolates tested were of intermediate magnitude and the ST252 isolate displayed the lowest pathogenic potential in all animal experiments. This ordering matched the genomic distance of the ST01 isolate to the non-ST01 isolates. Despite their close phylogenic relatedness, our results demonstrate differences in pathogenicity and virulence levels in Clade 2 C. difficile strains, confirm the high severity of infections caused by the NAP1/RT027/ST01 strain, and highlight the importance of C. difficile typing.
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影响因子：
3.1
作者：
Cavalcante, IC;Castro, MV;Brito, GAC
通讯作者：
Brito, GAC
影响因子：
3.7
作者：
Giel JL;Sorg JA;Sonenshein AL;Zhu J
通讯作者：
Zhu J
影响因子：
2.6
作者：
Janezic, Sandra;Rupnik, Maja
通讯作者：
Rupnik, Maja
影响因子：
2.3
作者：
Janoir, Claire
通讯作者：
Janoir, Claire
影响因子：
3.3
作者：
Dingle KE;Elliott B;Robinson E;Griffiths D;Eyre DW;Stoesser N;Vaughan A;Golubchik T;Fawley WN;Wilcox MH;Peto TE;Walker AS;Riley TV;Crook DW;Didelot X
通讯作者：
Didelot X