Cyclic AMP inhibits protein synthesis in Chlamydia trachomatis at a transcriptional level

Cyclic AMP (cAMP) has an inhibitory effect on the developmental cycle of Chlamydia trachomatis. We examined its influence on the synthesis of chlamydial protein, using the major outer membrane protein (MOMP) as a marker for general chlamydial protein synthesis. During normal development MOMP synthesis accelerates from 18 h post-infection and peaks by 36 h. Cyclic AMP blocks this normal progression of the chlamydial growth cycle. At a concentration of 1 mM, nearly 75% of the total MOMP synthesis was inhibited by 36 h, as monitored by radiolabel uptake. However, no difference was observed during the first 12 h between cAMP-treated and control groups, a finding which is in keeping with correlation between developmental inhibition and protein synthesis. Hybridization studies carried out with a cloned MOMP gene demonstrate a drastic decrease in MOMP mRNA in cAMP-treated cells. Low levels of cAMP utilized in conjunction with a 100,000 x g supernatant from reticulate bodies (RBs) blocked the transcription of the recombinant MOMP gene in an in vitro transcription system. These results suggest that the inhibition of chlamydial protein synthesis, assessed by MOMP synthesis, is due to regulation at a transcriptional level.