Differential transcriptional responses between the interferon-gamma-induction and iron-limitation models of persistence for Chlamydia pneumoniae.

Chlamydia spp. are important pathogens of humans and animals that cause a wide range of acute and chronic infections. A persistence model has been developed in which Chlamydia spp. do not complete their developmental cycle, have significantly reduced infectivity for new host cells, and exhibit abnormal inclusion and reticulate body morphology. This study was performed to compare the interferon-gamma (IFN-gamma) induction and iron-limitation models of persistence for Chlamydia spp. to investigate the common and unique transcriptional pathways involved.A quantitative real time-polymerase chain reaction approach was used to compare the IFN-gamma induction and iron-limitation models of Chlamydia pneumoniae persistence at the transcriptional level by analyzing selected genes in each of 5 distinct, functionally relevant subcategories.The models showed minimal evidence of a general transcriptional stress response in persistence, with only 1 of the 7 genes analyzed in the IFN-gamma induction model (htrA) and 4 of the genes in the iron-limitation model (htrA, clpB, clpP1, ahpC) showing increased mRNA levels. Both models showed similar responses in relation to the genes associated with lack of reticulate body to elementary body conversion (ctcB, lcrH1, and hctB levels were all unchanged or downregulated). The models also showed similar responses to the key cell wall/envelope genes, ompA, omcB, and crpA, exhibiting lower mRNA levels in both models.These data show that several key transcriptional pathways (lack of late developmental cycle completion, key cell wall components) respond similarly between the models. However, other pathways appear to differ depending on the persistence-inducing mechanism. This result suggests that Chlamydia spp. have evolved more than 1 mechanism to respond to different persistence-inducing conditions, but ultimately the pathways probably converge through a common persistence regulon.