IAI Accepts, published online ahead of print on 17 March 2008

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Infect. Immun. doi:10.1128/IAI.00102-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor

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

Laboratory of Intracellular Parasites, and Genomics Unit Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, 59840

^* To whom correspondence should be addressed. Email: hcaldwell{at}niaid.nih.gov.

Chlamydia trachomatis possess 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 L2 (25667R) strain was indistinguishable from the L2 (434) plasmid positive strain in 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 intra-inclusion Brownian-like movement characteristic of C. trachomatis strains. Conversely, we observed a marked difference between the two strains in their ability to colonize and infect the female mouse genital tract. The ID₅₀ of the L2 (25667R) plasmidless strain was 400 fold greater (4 x 10⁶ IFU) than the L2 (434) plasmid bearing strain (1 x 10⁴ IFU). Transcriptome analysis of the two strains demonstrated a decrease in transcript levels of a subset of chromosomal genes for the L2 (25667R) strain. 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 virulence is controlled, at least in part, by the plasmid's ability to regulate the expression of chromosomal genes. Our findings have important implications towards understanding a role for the plasmid in the pathogenesis of human infection and disease.