Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague

Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague
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DOI:
10.1073/pnas.0509544103
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发表时间:
2006-04-04
影响因子:
11.1
通讯作者:
Hinnebusch, BJ
Hinnebusch, BJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sebbane, F;Jarrett, CO;Hinnebusch, BJ

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鼠疫耶尔森氏菌通过跳蚤传播并引起黑死病,其特征是严重的局部淋巴结炎,并迅速发展为全身感染和危及生命的败血症。在这里,我们表明,虽然跳蚤传播的传播通常会导致小鼠鼠疫,但它也可能导致原发性败血性鼠疫。然而,皮内注射鼠疫耶尔森氏菌(通常用于模拟跳蚤传播)只会导致黑死病。缺乏质粒编码的细胞表面纤溶酶原激活剂的鼠疫耶尔森菌株,皮内或皮下注射无毒力。注射剂能够以低发病率引起致命的原发性败血性鼠疫,但当通过跳蚤传播时不会引起腺鼠疫。这些结果澄清了关于原发性败血性鼠疫病因学的长期不确定性,并支持了鼠疫最初作为一种传染性有限的跳蚤传播的败血病的进化情景。随后通过水平转移获得纤溶酶原激活剂基因,使疾病形成腺鼠疫形式,并增加了流行病传播的可能性。
Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread.