The Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis (CNFY) Enhances Inflammation and Yop Delivery during Infection by Activation of Rho GTPases.

2.50
Hdl Handle:
http://hdl.handle.net/10033/306430
Title:
The Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis (CNFY) Enhances Inflammation and Yop Delivery during Infection by Activation of Rho GTPases.
Authors:
Schweer, Janina; Kulkarni, Devesha; Kochut, Annika; Pezoldt, Joern; Pisano, Fabio; Pils, Marina C; Genth, Harald; Huehn, Jochen; Dersch, Petra ( 0000-0001-8177-3280 )
Abstract:
Some isolates of Yersinia pseudotuberculosis produce the cytotoxic necrotizing factor (CNFY), but the functional consequences of this toxin for host-pathogen interactions during the infection are unknown. In the present study we show that CNFY has a strong influence on virulence. We demonstrate that the CNFY toxin is thermo-regulated and highly expressed in all colonized lymphatic tissues and organs of orally infected mice. Most strikingly, we found that a cnfY knock-out variant of a naturally toxin-expressing Y. pseudotuberculosis isolate is strongly impaired in its ability to disseminate into the mesenteric lymph nodes, liver and spleen, and has fully lost its lethality. The CNFY toxin contributes significantly to the induction of acute inflammatory responses and to the formation of necrotic areas in infected tissues. The analysis of the host immune response demonstrated that presence of CNFY leads to a strong reduction of professional phagocytes and natural killer cells in particular in the spleen, whereas loss of the toxin allows efficient tissue infiltration of these immune cells and rapid killing of the pathogen. Addition of purified CNFY triggers formation of actin-rich membrane ruffles and filopodia, which correlates with the activation of the Rho GTPases, RhoA, Rac1 and Cdc42. The analysis of type III effector delivery into epithelial and immune cells in vitro and during the course of the infection further demonstrated that CNFY enhances the Yop translocation process and supports a role for the toxin in the suppression of the antibacterial host response. In summary, we highlight the importance of CNFY for pathogenicity by showing that this toxin modulates inflammatory responses, protects the bacteria from attacks of innate immune effectors and enhances the severity of a Yersinia infection.
Affiliation:
Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Citation:
The Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis (CNFY) Enhances Inflammation and Yop Delivery during Infection by Activation of Rho GTPases. 2013, 9 (11):e1003746 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Nov-2013
URI:
http://hdl.handle.net/10033/306430
DOI:
10.1371/journal.ppat.1003746
PubMed ID:
24244167
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the department of molecular Infectionbiology (MIBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchweer, Janinaen
dc.contributor.authorKulkarni, Deveshaen
dc.contributor.authorKochut, Annikaen
dc.contributor.authorPezoldt, Joernen
dc.contributor.authorPisano, Fabioen
dc.contributor.authorPils, Marina Cen
dc.contributor.authorGenth, Haralden
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorDersch, Petraen
dc.date.accessioned2013-12-06T12:52:25Zen
dc.date.available2013-12-06T12:52:25Zen
dc.date.issued2013-11en
dc.identifier.citationThe Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis (CNFY) Enhances Inflammation and Yop Delivery during Infection by Activation of Rho GTPases. 2013, 9 (11):e1003746 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid24244167en
dc.identifier.doi10.1371/journal.ppat.1003746en
dc.identifier.urihttp://hdl.handle.net/10033/306430en
dc.description.abstractSome isolates of Yersinia pseudotuberculosis produce the cytotoxic necrotizing factor (CNFY), but the functional consequences of this toxin for host-pathogen interactions during the infection are unknown. In the present study we show that CNFY has a strong influence on virulence. We demonstrate that the CNFY toxin is thermo-regulated and highly expressed in all colonized lymphatic tissues and organs of orally infected mice. Most strikingly, we found that a cnfY knock-out variant of a naturally toxin-expressing Y. pseudotuberculosis isolate is strongly impaired in its ability to disseminate into the mesenteric lymph nodes, liver and spleen, and has fully lost its lethality. The CNFY toxin contributes significantly to the induction of acute inflammatory responses and to the formation of necrotic areas in infected tissues. The analysis of the host immune response demonstrated that presence of CNFY leads to a strong reduction of professional phagocytes and natural killer cells in particular in the spleen, whereas loss of the toxin allows efficient tissue infiltration of these immune cells and rapid killing of the pathogen. Addition of purified CNFY triggers formation of actin-rich membrane ruffles and filopodia, which correlates with the activation of the Rho GTPases, RhoA, Rac1 and Cdc42. The analysis of type III effector delivery into epithelial and immune cells in vitro and during the course of the infection further demonstrated that CNFY enhances the Yop translocation process and supports a role for the toxin in the suppression of the antibacterial host response. In summary, we highlight the importance of CNFY for pathogenicity by showing that this toxin modulates inflammatory responses, protects the bacteria from attacks of innate immune effectors and enhances the severity of a Yersinia infection.en
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen
dc.titleThe Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis (CNFY) Enhances Inflammation and Yop Delivery during Infection by Activation of Rho GTPases.en
dc.contributor.departmentDepartment of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.en
dc.identifier.journalPLoS pathogensen

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