title: Toll-like receptor 2 activation by Chlamydia trachomatis is plasmid dependent, and plasmid-responsive chromosomal loci are coordinately regulated in response to glucose limitation by C. trachomatis but not by C. muridarum.
abstract: We previously demonstrated that plasmid-deficient Chlamydia muridarum retains the ability to infect the murine genital tract but does not elicit oviduct pathology because it fails to activate Toll-like receptor 2 (TLR2). We derived a plasmid-cured derivative of the human genital isolate Chlamydia trachomatis D/UW-3/Cx, strain CTD153, which also fails to activate TLR2, indicating this virulence phenotype is associated with plasmid loss in both C. trachomatis and C. muridarum. As observed with plasmid-deficient C. muridarum, CTD153 displayed impaired accumulation of glycogen within inclusions. Transcriptional profiling of the plasmid-deficient strains by using custom microarrays identified a conserved group of chromosomal loci, the expression of which was similarly controlled in plasmid-deficient C. muridarum strains CM972 and CM3.1 and plasmid-deficient C. trachomatis CTD153. However, although expression of glycogen synthase, encoded by glgA, was greatly reduced in CTD153, it was unaltered in plasmid-deficient C. muridarum strains. Thus, additional plasmid-associated factors are required for glycogen accumulation by this chlamydial species. Furthermore, in C. trachomatis, glgA and other plasmid-responsive chromosomal loci (PRCLs) were transcriptionally responsive to glucose limitation, indicating that additional regulatory elements may be involved in the coordinated expression of these candidate virulence effectors. Glucose-limited C. trachomatis displayed reduced TLR2 stimulation in an in vitro assay. During human chlamydial infection, glucose limitation may decrease chlamydial virulence through its effects on plasmid-responsive chromosomal genes.
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA. oconnellcm@upmc.edu
authors.forename: Catherine M
authors.initials: CM
authors.lastname: O'Connell
authors.forename: Yasser M
authors.initials: YM
authors.lastname: AbdelRahman
authors.forename: Erin
authors.initials: E
authors.lastname: Green
authors.forename: Hillary K
authors.initials: HK
authors.lastname: Darville
authors.forename: Kazima
authors.initials: K
authors.lastname: Saira
authors.forename: Bennett
authors.initials: B
authors.lastname: Smith
authors.forename: Toni
authors.initials: T
authors.lastname: Darville
authors.forename: Amy M
authors.initials: AM
authors.lastname: Scurlock
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Meyer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belland
mesh_terms: D000818:Animals; D002460:Cell Line; D002690:Chlamydia Infections / Q000235:genetics* / Q000378:metabolism; D023502:Chlamydia muridarum / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002692:Chlamydia trachomatis / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002876:Chromosomes, Bacterial / Q000235:genetics; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D056426:Genetic Loci; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D006003:Glycogen; D006006:Glycogen Synthase; D005947:Glucose