|
| Status |
Public on Feb 28, 2013 |
| Title |
The Chlamydia trachomatis plasmid-encoded Pgp4 is a transcriptional regulator of virulence associated chromosomal genes |
| Platform organisms |
Coxiella burnetii; Rickettsia rickettsii; Chlamydia muridarum; Chlamydia pneumoniae AR39; Staphylococcus epidermidis RP62A; Staphylococcus epidermidis ATCC 12228; Staphylococcus aureus subsp. aureus MW2; Borreliella burgdorferi B31; Coxiella burnetii RSA 493; Chlamydia caviae GPIC; Chlamydia trachomatis D/UW-3/CX; Staphylococcus haemolyticus JCSC1435; Granulibacter bethesdensis |
| Sample organism |
Chlamydia trachomatis |
| Experiment type |
Expression profiling by array
|
| Summary |
Chlamydia trachomatis causes chronic inflammatory diseases of the eye and genital tract of global medical importance. The chlamydial plasmid plays an important role in the pathophysiology of these diseases as plasmid-deficient organisms are highly attenuated. The plasmid encodes both noncoding RNAs and eight conserved ORFs of undefined function.
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 in terms of plasmid biology and transcriptional profiling.
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 plasmid-less strain in terms of abnormal inclusion morphology and lack of glycogen accumulation. Microarray and qRT-PCR analysis revealed that pgp4 is involved in transcriptional regulation of multiple chromosomal genes; including the glycogen synthase gene glgA. Based on our results, we propose that Pgp1 is a plasmid replicative helicase, Pgp2 is a plasmid replication protein, Pgp4 is a transcriptional regulator of virulence associated chromosomal genes, and Pgp6-8 are plasmid partitioning proteins. These findings have important implications for understanding the plasmid’s role in chlamydial pathogenesis and the development of novel antigenically multivalent live-attenuated chlamydial vaccines.
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| |
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| Overall design |
Chlamydia trachomatis wild type vs. two deletion mutants, and mock
|
| |
|
| Contributor(s) |
Song L, Carlson JH, Whitmire WM, Kari L, Virtaneva K, Sturdevant DE, Watkins H, Zhou B, Sturdevant GL, Porcella SF, Caldwell HD |
| Citation(s) |
23319558 |
| |
| Submission date |
Sep 19, 2012 |
| Last update date |
Apr 03, 2013 |
| Contact name |
Dan Sturdevant |
| E-mail(s) |
dsturdevant@niaid.nih.gov
|
| Phone |
4063639248
|
| Organization name |
NIH
|
| Department |
NIAID
|
| Lab |
RTS
|
| Street address |
903 S 4th street
|
| City |
Hamilton |
| State/province |
MT |
| ZIP/Postal code |
59840 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL4692 |
[RMLchip3a520351] Affymetrix RML Custom Pathogenic chip 3 |
|
| Samples (36)
|
|
| Relations |
| BioProject |
PRJNA175480 |
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