At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice
At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice
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DOI：
10.1128/iai.66.7.3372-3377.1998
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发表时间：
1998-07-01
影响因子：
3.1
通讯作者：
Kusters, JG
中科院分区：
文献类型：
--
作者：
Bowe, F;Lipps, CJ;Kusters, JG
鼠伤寒沙门氏菌感染是研究人类伤寒的一个已建立的模型系统。利用这个模型，我们确定了S。通过测试独立衍生的转座子插入突变体的体内毒力丧失，确定引起致命鼠感染所绝对需要的鼠伤寒沙门氏菌基因。在330株经腹腔注射和197株经灌胃试验的突变株中，鉴定出12株突变株的50%致死剂量大于亲本菌株的1，000倍。这些减毒突变体通过与已知毒力功能相关的体外试验来鉴定。此外，相应的转座子插入定位在S。获得了鼠伤寒沙门氏菌基因组和转座子侧翼DNA的核苷酸序列。沙门氏菌和相关细菌用侧翼DNA探测这些基因的存在。所有12个减毒突变体都在已知基因中插入，尽管先前仅描述了其中两个的减毒作用。此外，在本研究中获得的减毒突变体的比例表明，约4%的沙门氏菌基因组中的突变导致小鼠伤寒感染模型中的1,000倍或更大的减毒。这些基因中的大多数似乎在自然感染的早期阶段是必需的。
Salmonella typhimurium infection of mice is an established model system for studying typhoid fever in humans. Using this model, we identified S. typhimurium genes which are absolutely required to cause fatal murine infection by testing independently derived transposon insertion mutants for loss of virulence in vivo. Of the 330 mutants tested intraperitoneally and the 197 mutants tested intragastrically, 12 mutants with 50% lethal doses greater than 1,000 times that of the parental strain were identified. These attenuated mutants were characterized by in vitro assays which correlate with known virulence functions.;In addition, the corresponding transposon insertions were mapped within the S. typhimurium genome and the nucleotide sequence of the transposon-flanking DNA was obtained. Salmonella spp. and related bacteria were probed with flanking DNA for the presence of these genes. All 12 attenuated mutants had insertions in known genes, although the attenuating effects of only two of these were previously described. Furthermore, the proportion of attenuated mutants obtained in this study suggests that mutations in about 4% of the Salmonella genome lead to 1,000-fold or greater attenuation in the mouse typhoid model of infection. Most of these genes appear to be required during the early stages of a natural infection.