title: Chlamydia trachomatis plasmid-encoded Pgp4 is a transcriptional regulator of virulence-associated genes.
abstract: Chlamydia trachomatis causes chronic inflammatory diseases of the eye and genital tract and has global medical importance. The chlamydial plasmid plays an important role in the pathophysiology of these diseases, as plasmid-deficient organisms are highly attenuated. The cryptic plasmid carries noncoding RNAs and eight conserved open reading frames (ORFs). To understand plasmid gene function, we generated plasmid shuttle vectors with deletions in each of the eight ORFs. The individual deletion mutants were used to transform chlamydiae and the transformants were characterized phenotypically and at the transcriptional level. We show that pgp1, -2, -6, and -8 are essential for plasmid maintenance, while the other ORFs can be deleted and the plasmid stably maintained. We further show that a pgp4 knockout mutant exhibits an in vitro phenotype similar to its isogenic plasmidless strain, in terms of abnormal inclusion morphology and lack of glycogen accumulation. Microarray and qRT-PCR analysis revealed that Pgp4 is a transcriptional regulator of plasmid-encoded pgp3 and multiple chromosomal genes, including the glycogen synthase gene glgA, that are likely important in chlamydial virulence. Our findings have major implications for understanding the plasmid's role in chlamydial pathogenesis at the molecular level.
authors: Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
authors: Lihua
authors: L
authors: Song
authors: John H
authors: JH
authors: Carlson
authors: William M
authors: WM
authors: Whitmire
authors: Laszlo
authors: L
authors: Kari
authors: Kimmo
authors: K
authors: Virtaneva
authors: Daniel E
authors: DE
authors: Sturdevant
authors: Heather
authors: H
authors: Watkins
authors: Bing
authors: B
authors: Zhou
authors: Gail L
authors: GL
authors: Sturdevant
authors: Stephen F
authors: SF
authors: Porcella
authors: Grant
authors: G
authors: McClarty
authors: Harlan D
authors: HD
authors: Caldwell
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D002876:Chromosomes, Bacterial; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D051379:Mice; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D040081:Protein Array Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins