Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile

被引：11

作者：

Dong, Qiwen ^{[1
,2
]}

Lin, Huaiying ^{[2
]}

Allen, Marie-Maude ^{[3
]}

Garneau, Julian R. ^{[3
]}

Sia, Jonathan K. ^{[4
]}

Smith, Rita C. ^{[2
]}

Haro, Fidel ^{[2
]}

McMillen, Tracy ^{[5
]}

Pope, Rosemary L. ^{[2
,6
]}

Metcalfe, Carolyn ^{[2
]}

Burgo, Victoria ^{[2
]}

Woodson, Che ^{[2
]}

Dylla, Nicholas ^{[2
]}

Kohout, Claire ^{[2
]}

Sundararajan, Anitha ^{[2
]}

Snitkin, Evan S. ^{[7
]}

Young, Vincent B. ^{[7
,8
]}

Fortier, Louis-Charles ^{[3
]}

Kamboj, Mini ^{[5
]}

Pamer, Eric G. ^{[1
,2
,6
]}

机构：

[1] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[2] Univ Chicago, Duchossois Family Inst, Chicago, IL 60637 USA

[3] Univ Sherbrooke, Dept Microbiol & Infect Dis, Sherbrooke, PQ J1E 4K8, Canada

[4] Mem Sloan Kettering Canc Ctr, Immunol Program, New York, NY 10065 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Med, Infect Control, New York, NY 10065 USA

[6] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA

[7] Univ Michigan, Dept Internal Med, Div Infect Dis, Ann Arbor, MI 48109 USA

[8] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

来源：

CELL REPORTS | 2023年 / 42卷 / 08期

基金：

美国国家卫生研究院;

关键词：

TOXIN PRODUCTION; CD-HIT; GENE; INFECTION; STRAIN; BACTERIOPHAGES; PATHOGENICITY; EPIDEMIOLOGY; RIBOTYPE; DISEASE;

D O I：

10.1016/j.celrep.2023.112861

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains. We test 23 epidemic ST1 C. difficile clinical isolates for their virulence in mice. All isolates encode a complete Tcd pathogenicity locus and achieve similar colonization densities. However, disease severity varies from lethal to avirulent infections. Genomic analysis of avirulent isolates reveals a 69-bp deletion in the cdtR gene, which encodes a response regulator for binary toxin expression. Deleting the 69-bp sequence in virulent R20291 strain renders it avirulent in mice with reduced toxin gene transcription. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile isolates without reducing colonization and persistence. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis.

引用

页数：18

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