Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation.
Chlamydia trachomatis is an obligatory intracellular prokaryotic parasite that causes a spectrum of clinically important chronic inflammatory diseases of humans. Persistent infection may play a role in the pathophysiology of chlamydial disease. Here we describe the chlamydial transcriptome in an in vitro model of IFN-gamma-mediated persistence and reactivation from persistence. Tryptophan utilization, DNA repair and recombination, phospholipid utilization, protein translation, and general stress genes were up-regulated during persistence. Down-regulated genes included chlamydial late genes and genes involved in proteolysis, peptide transport, and cell division. Persistence was characterized by altered but active biosynthetic processes and continued replication of the chromosome. On removal of IFN-gamma, chlamydiae rapidly reentered the normal developmental cycle and reversed transcriptional changes associated with cytokine treatment. The coordinated transcriptional response to IFN-gamma implies that a chlamydial response stimulon has evolved to control the transition between acute and persistent growth of the pathogen. In contrast to the paradigm of persistence as a general stress response, our findings suggest that persistence is an alternative life cycle used by chlamydiae to avoid the host immune response.
Belland
Robert J
RJ
Laboratories of Intracellular Parasites and Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Nelson
David E
DE
Virok
Dezso
D
Crane
Deborah D
DD
Hogan
Daniel
D
Sturdevant
Daniel
D
Beatty
Wandy L
WL
Caldwell
Harlan D
HD
D002455:Cell Division; D002690:Chlamydia Infections; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects*
D012329:RNA, Bacterial; D007371:Interferon-gamma