Cianciotto N P, Eisenstein B I, Mody C H, Engleberg N C
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109.
J Infect Dis. 1990 Jul;162(1):121-6. doi: 10.1093/infdis/162.1.121.
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.
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。为了对此进行研究，在一个编码24000道尔顿表面蛋白的基因（mip）中引入了一个位点特异性突变；观察到该突变体对U937细胞和原代人肺泡巨噬细胞的感染力下降了80倍。对突变菌株的进一步表型分析未能显示出在毒力方面可能起作用的细菌因子（如蛋白酶、脂多糖）有改变。为了证实这种突变也会导致动物毒力降低，在豚鼠经气管内接种后，比较了亲本和突变嗜肺军团菌菌株所产生的致死率和临床病症。与亲本菌株或重新导入野生型mip基因的突变菌株衍生物相比，突变菌株引发的病症更少、疾病进展更慢且致死性感染更少。当使用这三种菌株的亚致死接种量时，在48小时时，从肺匀浆中回收的突变细菌数量略低于另外两种测试菌株，从脾脏中回收的数量则显著低于另外两种测试菌株。因此，mip似乎是嗜肺军团菌完全毒力所必需的，并且可能是该物种中第一个经基因定义的毒力因子。
