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Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection

Loss of the conserved “cryptic” plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital...

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Autores principales: Frazer, Lauren C., Darville, Toni, Chandra-Kuntal, Kumar, Andrews, Charles W., Zurenski, Matthew, Mintus, Margaret, AbdelRahman, Yasser M., Belland, Robert J., Ingalls, Robin R., O'Connell, Catherine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265510/
https://www.ncbi.nlm.nih.gov/pubmed/22292031
http://dx.doi.org/10.1371/journal.pone.0030747
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author Frazer, Lauren C.
Darville, Toni
Chandra-Kuntal, Kumar
Andrews, Charles W.
Zurenski, Matthew
Mintus, Margaret
AbdelRahman, Yasser M.
Belland, Robert J.
Ingalls, Robin R.
O'Connell, Catherine M.
author_facet Frazer, Lauren C.
Darville, Toni
Chandra-Kuntal, Kumar
Andrews, Charles W.
Zurenski, Matthew
Mintus, Margaret
AbdelRahman, Yasser M.
Belland, Robert J.
Ingalls, Robin R.
O'Connell, Catherine M.
author_sort Frazer, Lauren C.
collection PubMed
description Loss of the conserved “cryptic” plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains.
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spelling pubmed-32655102012-01-30 Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection Frazer, Lauren C. Darville, Toni Chandra-Kuntal, Kumar Andrews, Charles W. Zurenski, Matthew Mintus, Margaret AbdelRahman, Yasser M. Belland, Robert J. Ingalls, Robin R. O'Connell, Catherine M. PLoS One Research Article Loss of the conserved “cryptic” plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains. Public Library of Science 2012-01-24 /pmc/articles/PMC3265510/ /pubmed/22292031 http://dx.doi.org/10.1371/journal.pone.0030747 Text en Frazer et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Frazer, Lauren C.
Darville, Toni
Chandra-Kuntal, Kumar
Andrews, Charles W.
Zurenski, Matthew
Mintus, Margaret
AbdelRahman, Yasser M.
Belland, Robert J.
Ingalls, Robin R.
O'Connell, Catherine M.
Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection
title Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection
title_full Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection
title_fullStr Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection
title_full_unstemmed Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection
title_short Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection
title_sort plasmid-cured chlamydia caviae activates tlr2-dependent signaling and retains virulence in the guinea pig model of genital tract infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265510/
https://www.ncbi.nlm.nih.gov/pubmed/22292031
http://dx.doi.org/10.1371/journal.pone.0030747
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