Chlamydia trachomatis genes whose products are related to energy metabolism are expressed differentially in active vs. persistent infection.
The Chlamydia trachomatis genome encodes glycolysis and pentose phosphate pathway enzymes, two ATP/ADP exchange proteins, and other energy transduction-related components. We asked if and when chlamydial genes specifying products related to energy transduction are expressed during active vs. persistent infection in in vitro models and in synovia from Chlamydia-associated arthritis patients. Hep-2 cells infected with K serovar were harvested from 0-48 h post-infection (active infection). Human monocytes identically infected were harvested at 1, 2, 3, 5 days post-infection (persistent). RNA from each preparation and from synovial samples PCR-positive/-negative for Chlamydia DNA was subjected to RT-PCR targeting (a) chlamydial primary rRNA transcripts and adt1 mRNA, (b) chlamydial mRNA encoding enzymes of the glycolysis (pyk, gap, pgk) and pentose phosphate (gnd, tal) pathways, the TCA cycle (mdhC, fumC), electron transport system (cydA, cydB), and sigma factors (rpoD, rpsD, rpoN). Primary rRNA transcripts and adt1 mRNA were present in each infected preparation and patient sample; controls were negative for chlamydial RNA. In infected Hep-2 cells, all energy transduction-related genes were expressed by approximately 11 h post-infection. In monocytes, pyk, gap, pgk, gnd, tal, cydA mRNA were present in 1-2-day-infected cells but absent at 3 days and after; cydB, mdhC, fumC were expressed through 5 days post-infection. RT-PCR targeting mRNA from sigma factor genes indicated that lack of these gene products cannot explain selective transcriptional down-regulation during persistence. Analyses of RNA from synovial tissues mirrored those from the monocyte system. These data suggest that in the first phase of active chlamydial infection, ADP/ATP exchange provides energy required for metabolism; in active growth, glycolysis supplements host ATP. In persistence host, rather than bacterially produced, ATP is the primary energy source. Metabolic rate in persistent C. trachomatis is lower than in actively growing cells, as judged from assays for relative chlamydial primary rRNA transcript levels in persistent vs. actively growing cells.
Gérard
Hervé C
HC
Department of Immunology and Microbiology, Wayne State University School of Medicine, Gordon H. Scott Hall, 540 East Canfield Avenue, Detroit, MI 48201, USA.
Freise
Julia
J
Wang
Zhao
Z
Roberts
George
G
Rudy
Debbi
D
Krauss-Opatz
Birgit
B
Köhler
Lars
L
Zeidler
Henning
H
Schumacher
H Ralph
HR
Whittum-Hudson
Judith A
JA
Hudson
Alan P
AP
D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002690:Chlamydia Infections / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D002952:Citric Acid Cycle; D004579:Electron Transport; D004734:Energy Metabolism; D005798:Genes, Bacterial; D006019:Glycolysis; D006801:Humans; D010427:Pentose Phosphate Pathway; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000382:microbiology
D001426:Bacterial Proteins; D000255:Adenosine Triphosphate