Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
PLoS Pathog. 2010 Feb 26;6(2):e1000783. doi: 10.1371/journal.ppat.1000783.
Yersinia pestis, the agent of plague, is transmitted to mammals by infected fleas. Y. pestis exhibits a distinct life stage in the flea, where it grows in the form of a cohesive biofilm that promotes transmission. After transmission, the temperature shift to 37 degrees C induces many known virulence factors of Y. pestis that confer resistance to innate immunity. These factors are not produced in the low-temperature environment of the flea, however, suggesting that Y. pestis is vulnerable to the initial encounter with innate immune cells at the flea bite site. In this study, we used whole-genome microarrays to compare the Y. pestis in vivo transcriptome in infective fleas to in vitro transcriptomes in temperature-matched biofilm and planktonic cultures, and to the previously characterized in vivo gene expression profile in the rat bubo. In addition to genes involved in metabolic adaptation to the flea gut and biofilm formation, several genes with known or predicted roles in resistance to innate immunity and pathogenicity in the mammal were upregulated in the flea. Y. pestis from infected fleas were more resistant to phagocytosis by macrophages than in vitro-grown bacteria, in part attributable to a cluster of insecticidal-like toxin genes that were highly expressed only in the flea. Our results suggest that transit through the flea vector induces a phenotype that enhances survival and dissemination of Y. pestis after transmission to the mammalian host.
鼠疫耶尔森菌是鼠疫的病原体，通过受感染的跳蚤传播给哺乳动物。鼠疫耶尔森菌在跳蚤体内表现出明显的生命阶段，在那里它以一种促进传播的粘性生物膜形式生长。在传播后，温度向 37 摄氏度的转变会诱导鼠疫耶尔森菌的许多已知毒力因子，这些因子赋予其对先天免疫的抵抗力。然而，这些因子在跳蚤的低温环境中不会产生，这表明鼠疫耶尔森菌在跳蚤叮咬部位与先天免疫细胞的初次接触时很容易受到影响。在这项研究中，我们使用全基因组微阵列比较了感染性跳蚤体内的鼠疫耶尔森菌体内转录组与温度匹配的生物膜和浮游培养物中的体外转录组，以及以前在大鼠腹股沟淋巴结中表征的体内基因表达谱。除了参与代谢适应跳蚤肠道和生物膜形成的基因外，几个已知或预测在抵抗先天免疫和在哺乳动物中致病性方面具有作用的基因在跳蚤中上调。与体外生长的细菌相比，来自感染跳蚤的鼠疫耶尔森菌更能抵抗巨噬细胞的吞噬作用，部分原因是一组高度表达仅在跳蚤中表达的杀虫样毒素基因。我们的结果表明，通过跳蚤载体的转运诱导了一种表型，增强了鼠疫耶尔森菌在传播到哺乳动物宿主后的存活和传播能力。
