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Infection and Immunity, June 2008, p. 2273-2283, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00102-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Chlamydia trachomatis Plasmid Is a Transcriptional Regulator of Chromosomal Genes and a Virulence Factor ^,

John H. Carlson,^1, William M. Whitmire,^1, Deborah D. Crane,¹ Luke Wicke,² Kimmo Virtaneva,² Daniel E. Sturdevant,² John J. Kupko III,² Stephen F. Porcella,² Neysha Martinez-Orengo,² Robert A. Heinzen,¹ Laszlo Kari,¹ and Harlan D. Caldwell^1*

Laboratory of Intracellular Parasites,¹ Genomics Unit Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840²

Received 24 January 2008/ Returned for modification 25 February 2008/ Accepted 6 March 2008

Chlamydia trachomatis possesses a cryptic 7.5-kb plasmid of unknown function. Here, we describe a comprehensive molecular and biological characterization of the naturally occurring plasmidless human C. trachomatis strain L2(25667R). We found that despite minimal chromosomal polymorphisms, the LGV strain L2(25667R) was indistinguishable from plasmid-positive strain L2(434) with regard to its in vitro infectivity characteristics such as growth kinetics, plaquing efficiency, and plaque size. The only in vitro phenotypic differences between L2(434) and L2(25667R) were the accumulation of glycogen granules in the inclusion matrix and the lack of the typical intrainclusion Brownian-like movement characteristic of C. trachomatis strains. Conversely, we observed a marked difference between the two strains in their abilities to colonize and infect the female mouse genital tract. The 50% infective dose of plasmidless strain L2(25667R) was 400-fold greater (4 x 10⁶ inclusion-forming units [IFU]) than that of plasmid-bearing strain L2(434) (1 x 10⁴ IFU). Transcriptome analysis of the two strains demonstrated a decrease in the transcript levels of a subset of chromosomal genes for strain L2(25667R). Among those genes was glgA, encoding glycogen synthase, a finding consistent with the failure of L2(25667R) to accumulate glycogen granules. These findings support a primary role for the plasmid in in vivo infectivity and suggest that virulence is controlled, at least in part, by the plasmid's ability to regulate the expression of chromosomal genes. Our findings have important implications in understanding a role for the plasmid in the pathogenesis of human infection and disease.

Published ahead of print on 17 March 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: R. P. Morrison

J.H.C. and W.M.W. contributed equally to this work.