The obligate intracellular pathogen Chlamydia trachomatis, the leading cause of bacterial sexually transmitted infections, has a developmental cycle that differentiates between two functional and morphological forms, the elementary body (EB) and the reticulate body (RB).
The EB is the infectious and nondividing form that infects susceptible host cells. Once internalized into a host-derived vacuole called an inclusion, the EB differentiates into the non-infectious and replicating RB. At later stages of chlamydial development, RBs asynchronously undergo secondary differentiation creating new EBs. What host or bacterial factors function to trigger the differentiation from EBs to RBs and vice versa?
Dr. Vandana Singh, a postdoctoral trainee in Dr. Scot Ouellette’s laboratory, hypothesized that alterations in the bacterial redox status may be the differentiation trigger. Chlamydia lacks many common anti-oxidant enzymes but does have ahpC, a gene that encodes alkyl hydroperoxide reductase (AhpC). Genetic tools were designed to both knock down ahpC transcription or overexpress AhpC. Knock-down of ahpC increased susceptibility to peroxide stresses as predicted. However, EB-associated genes were also induced and a higher number of EBs were produced at an earlier time in the developmental cycle.
In contrast, AhpC overexpression resulted in delayed differentiation into EBs. How does the cellular redox status impact the developmental cycle? A model was proposed hypothesizing that oxidative stress linked to the metabolism of growth and replication functions to damage proteins, and accumulation of those proteins triggers differentiation from RBs to EBs.
Future studies are designed to identify redox sensitive proteins to understand mechanisms driving differentiation in Chlamydia. This study was published in the January edition of eLife.