In Vivo Germination of Bacillus anthracis Spores During Murine Cutaneous Infection

In Vivo Germination of Bacillus anthracis Spores During Murine Cutaneous Infection
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DOI:
10.1093/infdis/jis686
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发表时间:
2013-02-01
影响因子:
6.4
通讯作者:
Goossens, Pierre L.
Goossens, Pierre L.
中科院分区:
医学2区
文献类型:
--
作者:
Corre, Jean-Philippe;Piris-Gimenez, Alejandro;Goossens, Pierre L.

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背景资料。萌发是炭疽芽孢杆菌成功定植和系统传播的关键步骤。关于孢子在体内萌发的数据很少,孢子和寄主细胞相互作用启动萌发的必要性也不清楚。为了研究炭疽杆菌孢子与皮肤组织的早期相互作用,将孢子接种于豚鼠腹膜无细胞装置或小鼠耳廓内。通过菌落形成单位计数和电子显微镜对种子萌发和细菌生长情况进行分析。在豚鼠模型中,在没有细胞接触的情况下,体内发生了萌发。同样,在小鼠的耳朵中,接种后15分钟内开始萌发,在没有周围细胞的情况下发现了萌发的孢子。在富含巨噬细胞的引流淋巴结、肝和脾中未观察到萌发。由于缺乏毒素的菌株与类Sterne菌株一样有效,因此萌发不需要水肿和致命毒素的产生。炭疽杆菌生长被局部控制6h。不涉及细胞相互作用的孢子萌发可以在体内发生,这表明可扩散的萌发剂或其他信号似乎足够。不同寄主组织在萌发触发能力上表现出极大的差异。对细菌生长的初步控制表明,一种利用宿主固有防御来阻止炭疽杆菌定植的治疗方法。
Background. Germination is a key step for successful Bacillus anthracis colonization and systemic dissemination. Few data are available on spore germination in vivo, and the necessity of spore and host cell interactions to initiate germination is unclear.Methods. To investigate the early interactions between B. anthracis spores and cutaneous tissue, spores were inoculated in an intraperitoneal cell-free device in guinea pigs or into the pinna of mice. Germination and bacterial growth were analyzed through colony-forming unit enumeration and electron microscopy.Results. In the guinea pig model, germination occurred in vivo in the absence of cell contact. Similarly, in the mouse ear, germination started within 15 minutes after inoculation, and germinating spores were found in the absence of surrounding cells. Germination was not observed in macrophage-rich draining lymph nodes, liver, and spleen. Edema and lethal toxin production were not required for germination, as a toxin-deficient strain was as effective as a Sterne-like strain. B. anthracis growth was locally controlled for 6 hours.Conclusions. Spore germination involving no cell interactions can occur in vivo, suggesting that diffusible germinants or other signals appear sufficient. Different host tissues display drastic differences in germination-triggering capacity. Initial control of bacterial growth suggests a therapeutic means to exploit host innate defenses to hinder B. anthracis colonization.