Chlamydia trachomatis is a major cause of bacterial sexually transmitted infections. The regulation of gene expression in this important pathogen has not been well understood. Our long-range goals are to investigate the global regulatory mechanisms that allow C. trachomatis to survive in different conditions, as well as to persist in the host and contribute to human disease. We have demonstrated that the C. trachomatis alternative sigma factor, sigma 28, responds to heat shock and recognizes the hctB promoter of Chlamydia and also the fliC promoter of Escherichia coli. This suggests that sigma28 may be involved in transcription of a group of genes, which are required for an adaptation response enabling the successful completion of the developmental cycle. The objective of this proposal is to understand the biological function of one of the chlamydial sigma factors, sigma28, and to characterize its regulator(s). We propose two specific aims: 1) We will identify and characterize sigma28-dependent promoters and the sigma28 regulated target genes in C. trachomatis. We will also examine the activities of these promoters and their related target genes under conditions that are physiologically relevant for Chlamydia and 2) We will identify and characterize the putative regulator(s) of sigma28 in Chlamydia, and examine the effect on sigma28 specific transcription of interactions between sigma28 and its putative regulators. Information derived from these studies may lead to a better understanding of global regulation of genes, intracellular parasitism, virulence, immune evasion and persistence of C. trachomatis.
