title: Pathogenic diversity among Chlamydia trachomatis ocular strains in nonhuman primates is affected by subtle genomic variations.
abstract: Chlamydia trachomatis is the etiological agent of trachoma, the leading cause of preventable blindness. Trachoma presents distinct clinical syndromes ranging from mild and self-limiting to severe inflammatory disease. The underlying host and pathogen factors responsible for these diverse clinical outcomes are unclear. To assess the role played by pathogen variation in disease outcome, we analyzed the genomes of 4 trachoma strains representative of the 3 major trachoma serotypes, using microarray-based comparative genome sequencing. Outside of ompA, trachoma strains differed primarily in a very small subset of genes (n = 22). These subtle genetic variations were manifested in profound differences in virulence as measured by in vitro growth rate, burst size, plaque morphology, and interferon-gamma sensitivity but most importantly in virulence as shown by ocular infection of nonhuman primates. Our findings are the first to identify genes that correlate with differences in pathogenicity among trachoma strains.
authors.affiliation: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kari
authors.forename: William M
authors.initials: WM
authors.lastname: Whitmire
authors.forename: John H
authors.initials: JH
authors.lastname: Carlson
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Crane
authors.forename: Nathalie
authors.initials: N
authors.lastname: Reveneau
authors.forename: David E
authors.initials: DE
authors.lastname: Nelson
authors.forename: David C W
authors.initials: DC
authors.lastname: Mabey
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bailey
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Holland
authors.forename: Grant
authors.initials: G
authors.lastname: McClarty
authors.forename: Harlan D
authors.initials: HD
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D002692:Chlamydia trachomatis / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D014644:Genetic Variation; D016680:Genome, Bacterial; D006367:HeLa Cells; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D011110:Polymorphism, Genetic; D011323:Primates / Q000382:microbiology*; D014141:Trachoma / Q000382:microbiology