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PNAS 109 (26): 10546-10551

Copyright © 2012 by the National Academy of Sciences.


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

Christopher C. Thompsona,1, Sophie S. Nicoda, Denise S. Malcolma, Scott S. Grieshaberb, and Rey A. Carabeoa,2

aMedical Research Council (MRC) Centre for Molecular Bacteriology and Infection, Division of Cell and Molecular Biology, Imperial College, London SW7 2AZ, United Kingdom; and bDepartment of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610

Edited by E. Peter Greenberg, University of Washington, Seattle, WA, and approved May 16, 2012 (received for review January 25, 2012)

Abstract: 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.

Key Words: fusion-protein • ABC-3 permease • metalloregulation • autorepression

Author contributions: C.C.T. and R.A.C. designed research; C.C.T., S.S.N., D.S.M., and S.S.G. performed research; S.S.G. contributed new reagents/analytic tools; C.C.T., S.S.N., D.S.M., S.S.G., and R.A.C. analyzed data; and C.C.T. and R.A.C. wrote the paper.

1Present address: Jefferiss Research Trust Laboratories, Division of Infectious Diseases, Imperial College, London W2 1PG, United Kingdom.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at

2To whom correspondence should be addressed. E-mail: r.carabeo{at}

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