Affiliation:
1. Department of Microbiology and Molecular Genetics
2. Department of Medicine, School of Medicine, University of California, Irvine, California 92697-4025
Abstract
ABSTRACT
Tryptophan is an essential amino acid that is required for normal development in
Chlamydia
species, and tryptophan metabolism has been implicated in chlamydial persistence and tissue tropism. The ability to synthesize tryptophan is not universal among the
Chlamydiaceae
, but species that have a predicted tryptophan biosynthetic pathway also encode an ortholog of TrpR, a regulator of tryptophan metabolism in many gram-negative bacteria. We show that in
Chlamydia trachomatis
serovar D, TrpR regulates its own gene and
trpB
and
trpA
, the genes for the two subunits of tryptophan synthase. These three genes form an operon that is transcribed by the major form of chlamydial RNA polymerase. TrpR acts as a tryptophan-dependent aporepressor that binds specifically to operator sequences upstream of the
trpRBA
operon. We also found that TrpR repressed in vitro transcription of
trpRBA
in a promoter-specific manner, and the level of repression was dependent upon the concentrations of TrpR and tryptophan. Our findings provide a mechanism for chlamydiae to sense changes in tryptophan levels and to respond by modulating expression of the tryptophan biosynthesis genes, and we present a unified model that shows how
C. trachomatis
can combine transcriptional repression and attenuation to regulate intrachlamydial tryptophan levels. In the face of host defense mechanisms that limit tryptophan availability from the infected cell, the ability to maintain homeostatic control of intrachlamydial tryptophan levels is likely to play an important role in chlamydial pathogenesis.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
60 articles.
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