A MUTATION IN THE MIP GENE RESULTS IN AN ATTENUATION OF LEGIONELLA-PNEUMOPHILA VIRULENCE
A MUTATION IN THE MIP GENE RESULTS IN AN ATTENUATION OF LEGIONELLA-PNEUMOPHILA VIRULENCE
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DOI：
10.1093/infdis/162.1.121
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发表时间：
1990-07-01
影响因子：
6.4
通讯作者：
ENGLEBERG, NC
中科院分区：
文献类型：
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作者：
CIANCIOTTO, NP;EISENSTEIN, BI;ENGLEBERG, NC
嗜肺军团菌的感染被认为取决于其在宿主肺泡巨噬细胞内繁殖的能力。为了研究这一点，将位点特异性突变引入编码24，000-Da表面蛋白的基因（mip）中;观察到U937细胞和灭活的人肺泡巨噬细胞的感染性损失80倍。突变菌株的进一步表型分析未能显示细菌因子的改变（例如，蛋白酶、脂多糖），其在毒力中具有可疑作用。为了证实这种突变也会导致动物毒力降低，研究了亲本和突变体L.在豚鼠体内接种后比较嗜肺菌菌株。与亲本菌株或重新引入野生型mip基因的突变菌株衍生物相比，突变菌株产生的疾病更少，疾病进展更慢，致命感染更少。当亚致死接种的三种菌株被使用时，突变体细菌被回收的数量略低，从肺匀浆和显着较低的数量从脾脏，在48小时，比其他两个测试菌株。因此mip可能是L. pneumophila，并可能代表第一个遗传定义的毒力因子在这个物种。
Infection by Legionella pneumophila is believed to depend upon its ability to multiply within host alveolar macrophages. To investigate this, a site-specific mutation was introduced into a gene (mip) that encodes a 24,000-Da surface protein; an 80-fold loss of infectivity for both U937 cells and explanted human alveolar macrophages was observed. Further phenotypic analysis of the mutant strain has failed to show alterations in bacterial factors (e.g., proteinase, lipopolysaccharide) that have suspected roles in virulence. To substantiate that this mutation also results in reduced virulence in animals, the lethality and clinical illnesses produced by the parent and mutant L. pneumophila strains were compared in guinea pigs after intratracheal inoculation. The mutant strain produced fewer illnesses, slower-progressing disease, and fewer lethal infections than either the parent strain or a derivative of the mutant strain with the wild-type mip gene reintroduced. When sublethal inocula of the three strains were used, the mutant bacteria were recovered in slightly lower numbers from lung homogenates and in significantly lower numbers from the spleen, at 48 h, than were the other two test strains. Thus mip seems to be necessary for full virulence of L. pneumophila and may represent the first genetically defined virulence factor in this species.