Abstract

Chlamydia trachomatis causes inflammatory diseases of the eye and genital tract of global importance. Its cryptic plasmid is a key virulence factor in chlamydial pathogenicity. Infections produced by plasmid-cured organisms are short-lived, resolve without measurable pathology, and paradoxically induce superior levels of protective immunity. To better understand the function of plasmid genes we made deletion mutants of all 8 plasmid genes and characterized the gene functions in plasmid biology and pathogenesis. We show that Pgp4 controls the transcription of multiple chlamydial chromosomal genes including those that function in glycogen biosynthesis and type I interferon signaling. Notably, chlamydial glycogen was found to be a ligand for the production of IL-10 by human dendritic cells. Collectively, the findings support a role for Pgp4-regulated chromosomal genes as mediators of inflammation and modulators of T-cell immunity that offer a plausible explanation for the attenuation and superior protective immunogenicity of plasmid-deficient organisms.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI000845-14
Application #
8555838
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2012
Total Cost
$867,771
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Patton, Michael John; Chen, Chih-Yu; Yang, Chunfu et al. (2018) Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive Chlamydia trachomatis Biovars. MBio 9:
Patton, Dorothy L; Sweeney, Yvonne C; Baldessari, Audrey E et al. (2018) The Chlamydia trachomatis Plasmid and CT135 Virulence Factors Are Not Essential for Genital Tract Infection or Pathology in Female Pig-Tailed Macaques. Infect Immun 86:
Yang, Chunfu; Kari, Laszlo; Sturdevant, Gail L et al. (2017) Chlamydia trachomatis ChxR is a transcriptional regulator of virulence factors that function in in vivo host-pathogen interactions. Pathog Dis 75:
Yang, Chunfu; Whitmire, William M; Sturdevant, Gail L et al. (2017) Infection of Hysterectomized Mice with Chlamydia muridarum and Chlamydia trachomatis. Infect Immun 85:
Patton, Michael John; McCorrister, Stuart; Grant, Chris et al. (2016) Chlamydial Protease-Like Activity Factor and Type III Secreted Effectors Cooperate in Inhibition of p65 Nuclear Translocation. MBio 7:
Porcella, Stephen F; Carlson, John H; Sturdevant, Daniel E et al. (2015) Transcriptional profiling of human epithelial cells infected with plasmid-bearing and plasmid-deficient Chlamydia trachomatis. Infect Immun 83:534-43
Song, Lihua; Carlson, John H; Zhou, Bing et al. (2014) Plasmid-mediated transformation tropism of chlamydial biovars. Pathog Dis 70:189-93
Bao, Xiaofeng; Gylfe, Asa; Sturdevant, Gail L et al. (2014) Benzylidene acylhydrazides inhibit chlamydial growth in a type III secretion- and iron chelation-independent manner. J Bacteriol 196:2989-3001
Sturdevant, Gail L; Caldwell, Harlan D (2014) Innate immunity is sufficient for the clearance of Chlamydia trachomatis from the female mouse genital tract. Pathog Dis 72:70-3
Kari, Laszlo; Southern, Timothy R; Downey, Carey J et al. (2014) Chlamydia trachomatis polymorphic membrane protein D is a virulence factor involved in early host-cell interactions. Infect Immun 82:2756-62

Showing the most recent 10 out of 24 publications