Cleavage of a putative metal permease in Chlamydia trachomatis yields an iron-dependent transcriptional repressor

• Published in: Proceedings of the National Academy of Sciences - PNAS 2012-06, Vol.109 (26), p.10546-10551
• Main Authors: Thompson, Christopher C, Nicod, Sophie S, Malcolm, Denise S, Grieshaber, Scott S, Carabeo, Rey A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; bacteria; Binding sites; biochemical pathways; Biological Sciences; Chlamydia; Chlamydia trachomatis; Chlamydia trachomatis - enzymology; Escherichia coli; Gene expression; Gram-negative bacteria; homeostasis; humans; Iron; Iron - metabolism; Mathematical vectors; Membrane transport proteins; Membranes; Models, Molecular; Molecular Sequence Data; Operon; Operons; pathogens; Plasmids; polypeptides; Proteins; Proteolysis; Reporter genes; repressor proteins; Repressor Proteins - chemistry; Repressor Proteins - metabolism; Sequence Homology, Amino Acid; starvation; toxicity; Transcription, Genetic; Transcriptional regulatory elements
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1201398109

The regulation of iron homeostasis is essential for most organisms, because iron is required for a variety of conserved biochemical processes, yet can be toxic at high concentrations. Upon experiencing iron starvation in vitro, the obligate intracellular human pathogen Chlamydia trachomatis exhibits elevated expression of a putative iron-transport system encoded by the ytg operon. The third component of the ytg operon, CT069 (YtgCR), encodes a protein with two distinct domains: a membrane-anchored metal ion permease and a diphtheria toxin repressor (DtxR)-like transcriptional repressor. In this report, we demonstrate that the C-terminal domain of CT069 (YtgR) serves as an iron-dependent autorepressor of the ytg operon. Moreover, the nascent full-length metal permease-transcriptional repressor protein was processed during the course of infection, and heterologously when expressed in Escherichia coli . The products produced by heterologous cleavage in E. coli were functional in the repression of a reporter gene downstream of a putative YtgR operator. We report a bona fide mechanism of iron-dependent regulation of transcription in Chlamydia . Moreover, the unusual membrane permease-DNA-binding polypeptide fusion configuration was found in several bacteria. Therefore, the DNA-binding capability and liberation of the YtgR domain from a membrane-anchored permease in C. trachomatis could represent a previously uncharacterized mechanism for prokaryotic regulation of iron-homeostasis.