title: Plasmid CDS5 influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection.
abstract: The native plasmid of both Chlamydia muridarum and Chlamydia trachomatis has been shown to control virulence and infectivity in mice and in lower primates. We recently described the development of a plasmid-based genetic transformation protocol for Chlamydia trachomatis that for the first time provides a platform for the molecular dissection of the function of the chlamydial plasmid and its individual genes or coding sequences (CDS). In the present study, we transformed a plasmid-free lymphogranuloma venereum isolate of C. trachomatis, serovar L2, with either the original shuttle vector (pGFP::SW2) or a derivative of pGFP::SW2 carrying a deletion of the plasmid CDS5 gene (pCDS5KO). Female mice were inoculated with these strains either intravaginally or transcervically. We found that transformation of the plasmid-free isolate with the intact pGFP::SW2 vector significantly enhanced infectivity and induction of host inflammatory responses compared to the plasmid-free parental isolate. Transformation with pCDS5KO resulted in infection courses and inflammatory responses not significantly different from those observed in mice infected with the plasmid-free isolate. These results indicate a critical role of plasmid CDS5 in in vivo fitness and in induction of inflammatory responses. To our knowledge, these are the first in vivo observations ascribing infectivity and virulence to a specific plasmid gene.
authors.affiliation: Department of Microbiology & Immunology, Chicago College of Osteopathic Medicine, Illinois Midwestern University, Downers Grove, Illinois, USA kramse@midwestern.edu.
authors.forename: K H
authors.initials: KH
authors.lastname: Ramsey
authors.affiliation: Department of Microbiology & Immunology, Chicago College of Osteopathic Medicine, Illinois Midwestern University, Downers Grove, Illinois, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Schripsema
authors.affiliation: Department of Microbiology & Immunology, Chicago College of Osteopathic Medicine, Illinois Midwestern University, Downers Grove, Illinois, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: Department of Clinical and Experimental Sciences, Molecular Microbiology Group, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Dental Medicine, Illinois Midwestern University, Downers Grove, Illinois, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Jham
authors.affiliation: Department of Physiology, Chicago College of Osteopathic Medicine, Illinois Midwestern University, Downers Grove, Illinois, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: O'Hagan
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: N R
authors.initials: NR
authors.lastname: Thomson
authors.affiliation: Department of Pathology, Chicago College of Osteopathic Medicine, Illinois Midwestern University, Downers Grove, Illinois, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Murthy
authors.affiliation: Department of Clinical and Experimental Sciences, Molecular Microbiology Group, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Skilton
authors.affiliation: Department of Microbiology & Immunology, Chicago College of Osteopathic Medicine, Illinois Midwestern University, Downers Grove, Illinois, USA.
authors.forename: P
authors.initials: P
authors.lastname: Chu
authors.affiliation: Department of Clinical and Experimental Sciences, Molecular Microbiology Group, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: I N
authors.initials: IN
authors.lastname: Clarke
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002690:Chlamydia Infections / Q000382:microbiology* / Q000473:pathology*; D002692:Chlamydia trachomatis / Q000235:genetics / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D008219:Lymphogranuloma Venereum / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D010957:Plasmids; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors