Kari Laszlo, Whitmire William M, Carlson John H, Crane Deborah D, Reveneau Nathalie, Nelson David E, Mabey David C W, Bailey Robin L, Holland Martin J, McClarty Grant, Caldwell Harlan D
Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
J Infect Dis. 2008 Feb 1;197(3):449-56. doi: 10.1086/525285.
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.
沙眼衣原体是沙眼的病原体，沙眼是可预防失明的主要原因。沙眼呈现出从轻度自限性到严重炎症性疾病的不同临床综合征。导致这些不同临床结果的潜在宿主和病原体因素尚不清楚。为了评估病原体变异在疾病结果中所起的作用，我们使用基于微阵列的比较基因组测序分析了代表3种主要沙眼血清型的4株沙眼菌株的基因组。除ompA外，沙眼菌株主要在极少数基因子集（n = 22）上存在差异。这些细微的基因变异表现为体外生长速率、爆发量、噬菌斑形态和干扰素-γ敏感性所衡量的毒力上的显著差异，但最重要的是在非人灵长类动物眼部感染所显示的毒力上的差异。我们的发现首次鉴定出与沙眼菌株致病性差异相关的基因。
