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Infection and Immunity, October 2005, p. 6407-6418, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6407-6418.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative Genomic Analysis of Chlamydia trachomatis Oculotropic and Genitotropic Strains{dagger}

John H. Carlson,1 Stephen F. Porcella,2 Grant McClarty,3 and Harlan D. Caldwell1*

Laboratory of Intracellular Parasites,1 Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, Montana, 59840,2 Department of Medical Microbiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada, R3E 0W33

Received 31 March 2005/ Returned for modification 16 May 2005/ Accepted 2 June 2005

Chlamydia trachomatis infection is an important cause of preventable blindness and sexually transmitted disease (STD) in humans. C. trachomatis exists as multiple serovariants that exhibit distinct organotropism for the eye or urogenital tract. We previously reported tissue-tropic correlations with the presence or absence of a functional tryptophan synthase and a putative GTPase-inactivating domain of the chlamydial toxin gene. This suggested that these genes may be the primary factors responsible for chlamydial disease organotropism. To test this hypothesis, the genome of an oculotropic trachoma isolate (A/HAR-13) was sequenced and compared to the genome of a genitotropic (D/UW-3) isolate. Remarkably, the genomes share 99.6% identity, supporting the conclusion that a functional tryptophan synthase enzyme and toxin might be the principal virulence factors underlying disease organotropism. Tarp (translocated actin-recruiting phosphoprotein) was identified to have variable numbers of repeat units within the N and C portions of the protein. A correlation exists between lymphogranuloma venereum serovars and the number of N-terminal repeats. Single-nucleotide polymorphism (SNP) analysis between the two genomes highlighted the minimal genetic variation. A disproportionate number of SNPs were observed within some members of the polymorphic membrane protein (pmp) autotransporter gene family that corresponded to predicted T-cell epitopes that bind HLA class I and II alleles. These results implicate Pmps as novel immune targets, which could advance future chlamydial vaccine strategies. Lastly, a novel target for PCR diagnostics was discovered that can discriminate between ocular and genital strains. This discovery will enhance epidemiological investigations in nations where both trachoma and chlamydial STD are endemic.

* Corresponding author. Mailing address: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, Montana, 59840. Phone: (406) 363-9333. Fax: (406) 363-9380. E-mail: hcaldwell{at}niaid.nih.gov.

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

Editor: J. B. Bliska

Infection and Immunity, October 2005, p. 6407-6418, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6407-6418.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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