title: Chlamydia trachomatis ChxR is a transcriptional regulator of virulence factors that function in in vivo host-pathogen interactions.
abstract: Chlamydia trachomatis is an obligate intracellular pathogen characterized by a unique biphasic developmental cycle that alternates between infectious and non-infectious organisms. Chlamydial ChxR is a transcriptional activator that has been implicated in the regulation of the development cycle. We used a reverse genetics approach to generate three chxR null mutants. All three mutants grew normally in cultured mammalian cells. Whole genome sequencing identified SNPs in other genes; however, none of the mutated genes were common to all three ChxR null mutants arguing against a genetic compensatory mechanism that would explain the non-essential in vitro growth phenotype. Comparative proteomics identified five proteins, CT005, CT214, CT565, CT694 and CT695, that were significantly downregulated in all ChxR null mutants. This group includes established inclusion membrane and type III secreted proteins. ChxR transcriptional regulation of these genes was confirmed by qRT-PCR. Importantly, while ChxR null mutants exhibited no growth deficiencies in in vitro, they did show significant differences in in vivo growth using a mouse genital tract model. Collectively, our findings demonstrated that ChxR is a transcriptional activator that regulates the expression of virulence genes whose functions are restricted to in vivo infection.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-6612, USA.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Yang
authors.affiliation: Laboratory of Bacteriology, National Institute of Allergy and Infectious Disease, Rocky Mountain Laboratory, Hamilton, MT 59840, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kari
authors.affiliation: Laboratory of Virology, National Institute of Allergy and Infectious Disease, Hamilton, MT 59840, USA.
authors.forename: Gail L
authors.initials: GL
authors.lastname: Sturdevant
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Beijing 100039, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Song
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-6612, USA.
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Patton
authors.affiliation: Laboratory of Bacteriology, National Institute of Allergy and Infectious Disease, Rocky Mountain Laboratory, Hamilton, MT 59840, USA.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Couch
authors.affiliation: Laboratory of Bacteriology, National Institute of Allergy and Infectious Disease, Rocky Mountain Laboratory, Hamilton, MT 59840, USA.
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Ilgenfritz
authors.affiliation: Laboratory of Bacteriology, National Institute of Allergy and Infectious Disease, Rocky Mountain Laboratory, Hamilton, MT 59840, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Southern
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-6612, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Whitmire
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-6612, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Briones
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Bonner
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Grant
authors.affiliation: Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg R3E 3R2, Canada.
authors.forename: Pinzhao
authors.initials: P
authors.lastname: Hu
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
authors.forename: Grant
authors.initials: G
authors.lastname: McClarty
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-6612, USA.
authors.forename: Harlan D
authors.initials: HD
authors.lastname: Caldwell
mesh_terms: D000483:Alleles; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002690:Chlamydia Infections / Q000235:genetics* / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D016680:Genome, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D009154:Mutation; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D037521:Virulence Factors
keywords: Chlamydia; ChxR; in vivo infection; transcription