The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia

Research output: Contribution to journalArticlepeer-review

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The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia. / Cowardin, Carrie A; Buonomo, Erica L; Saleh, Mahmoud M; Wilson, Madeline G; Burgess, Stacey L; Kuehne, Sarah A; Schwan, Carsten; Eichhoff, Anna M; Koch-Nolte, Friedrich; Lyras, Dena; Aktories, Klaus; Minton, Nigel P; Petri, William A.

In: Nature Microbiology, Vol. 1, No. 8, 16108, 11.07.2016.

Research output: Contribution to journalArticlepeer-review

Harvard

Cowardin, CA, Buonomo, EL, Saleh, MM, Wilson, MG, Burgess, SL, Kuehne, SA, Schwan, C, Eichhoff, AM, Koch-Nolte, F, Lyras, D, Aktories, K, Minton, NP & Petri, WA 2016, 'The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia', Nature Microbiology, vol. 1, no. 8, 16108. https://doi.org/10.1038/nmicrobiol.2016.108

APA

Cowardin, C. A., Buonomo, E. L., Saleh, M. M., Wilson, M. G., Burgess, S. L., Kuehne, S. A., Schwan, C., Eichhoff, A. M., Koch-Nolte, F., Lyras, D., Aktories, K., Minton, N. P., & Petri, W. A. (2016). The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia. Nature Microbiology, 1(8), [16108]. https://doi.org/10.1038/nmicrobiol.2016.108

Vancouver

Author

Cowardin, Carrie A ; Buonomo, Erica L ; Saleh, Mahmoud M ; Wilson, Madeline G ; Burgess, Stacey L ; Kuehne, Sarah A ; Schwan, Carsten ; Eichhoff, Anna M ; Koch-Nolte, Friedrich ; Lyras, Dena ; Aktories, Klaus ; Minton, Nigel P ; Petri, William A. / The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia. In: Nature Microbiology. 2016 ; Vol. 1, No. 8.

Bibtex

@article{90f286f9b9684acabd30a4a8f1b13f4d,
title = "The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia",
abstract = "Clostridium difficile is the most common hospital acquired pathogen in the USA, and infection is, in many cases, fatal. Toxins A and B are its major virulence factors, but expression of a third toxin, known as C. difficile transferase (CDT), is increasingly common. An adenosine diphosphate (ADP)-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. Here, we show that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a Toll-like receptor 2 (TLR2)-dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, we show that restoration of TLR2-deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C. difficile and demonstrate a mechanism by which this binary toxin subverts the host immune response.",
keywords = "Journal Article",
author = "Cowardin, {Carrie A} and Buonomo, {Erica L} and Saleh, {Mahmoud M} and Wilson, {Madeline G} and Burgess, {Stacey L} and Kuehne, {Sarah A} and Carsten Schwan and Eichhoff, {Anna M} and Friedrich Koch-Nolte and Dena Lyras and Klaus Aktories and Minton, {Nigel P} and Petri, {William A}",
year = "2016",
month = jul,
day = "11",
doi = "10.1038/nmicrobiol.2016.108",
language = "English",
volume = "1",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",
number = "8",

}

RIS

TY - JOUR

T1 - The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia

AU - Cowardin, Carrie A

AU - Buonomo, Erica L

AU - Saleh, Mahmoud M

AU - Wilson, Madeline G

AU - Burgess, Stacey L

AU - Kuehne, Sarah A

AU - Schwan, Carsten

AU - Eichhoff, Anna M

AU - Koch-Nolte, Friedrich

AU - Lyras, Dena

AU - Aktories, Klaus

AU - Minton, Nigel P

AU - Petri, William A

PY - 2016/7/11

Y1 - 2016/7/11

N2 - Clostridium difficile is the most common hospital acquired pathogen in the USA, and infection is, in many cases, fatal. Toxins A and B are its major virulence factors, but expression of a third toxin, known as C. difficile transferase (CDT), is increasingly common. An adenosine diphosphate (ADP)-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. Here, we show that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a Toll-like receptor 2 (TLR2)-dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, we show that restoration of TLR2-deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C. difficile and demonstrate a mechanism by which this binary toxin subverts the host immune response.

AB - Clostridium difficile is the most common hospital acquired pathogen in the USA, and infection is, in many cases, fatal. Toxins A and B are its major virulence factors, but expression of a third toxin, known as C. difficile transferase (CDT), is increasingly common. An adenosine diphosphate (ADP)-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. Here, we show that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a Toll-like receptor 2 (TLR2)-dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, we show that restoration of TLR2-deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C. difficile and demonstrate a mechanism by which this binary toxin subverts the host immune response.

KW - Journal Article

U2 - 10.1038/nmicrobiol.2016.108

DO - 10.1038/nmicrobiol.2016.108

M3 - Article

C2 - 27573114

VL - 1

JO - Nature Microbiology

JF - Nature Microbiology

SN - 2058-5276

IS - 8

M1 - 16108

ER -