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Infection and Immunity, December 2004, p. 7063-7072, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.7063-7072.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Polymorphisms in the Chlamydia trachomatis Cytotoxin Locus Associated with Ocular and Genital Isolates

John H. Carlson,1 Scott Hughes,1 Daniel Hogan,2 Gordon Cieplak,1 Daniel E. Sturdevant,2 Grant McClarty,3 Harlan D. Caldwell,1 and Robert J. Belland1*

Laboratory of Intracellular Parasites,1 Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana,2 Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada3

Received 30 July 2004/ Returned for modification 20 August 2004/ Accepted 26 August 2004

Chlamydia trachomatis is a strict human pathogen producing infections that cause medically important chronic inflammatory diseases, such as blinding trachoma and tubal factor infertility. Isolates exist as serotypes that fall into distinct biologic and pathological groups corresponding to differences in infection tissue tropism and invasion properties. Paradoxically, genome sequencing of several diverse strains has revealed a remarkable level of genomic synteny, suggesting that minor genetic differences determine the pathogen host- and tissue-specific infection characteristics. To better understand the genetic basis of chlamydial pathobiologic diversity, we performed comparative DNA-DNA microarray genomic hybridizations with all 15 C. trachomatis serovariants. We found there are few major genetic differences among the 15 serovars. An exception was the cytotoxin locus located in the plasticity zone, a region that exhibited significant polymorphisms among serovars. We therefore sequenced this region from all 15 serovars. The cytotoxin gene was interrupted by extensive mutations and deletions among the different serovars; however, three basic open reading frame motifs were discovered that correlated with noninvasive oculotropic, urogenitotropic, and invasive serovars. Of interest, only noninvasive genitotropic serovars possessed an intact N-terminal portion of the putative toxin gene. This region contains the UDP-glucose binding domain and the glycosyltransferase domain required for enzymatic activity of the clostridial toxin homologs, suggesting a role in urogenital infection or pathogenesis.

* Corresponding author. Present address: University of Tennessee, Memphis Health Science Center, College of Medicine, Department of Molecular Science, 858 Madison Ave., Memphis, TN 38163. Phone: (901) 448-8544. Fax: (901) 448-8462. E-mail: rbelland{at}UTMEM.edu.

Editor: D. L. Burns

Infection and Immunity, December 2004, p. 7063-7072, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.7063-7072.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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