Stocker B A, Hoiseth S K, Smith B P
Dev Biol Stand. 1983;53:47-54.
A block in the common aromatic biosynthesis (aro) pathway makes E. coli, Salmonella, etc., exacting for aromatic metabolites; two of these, paraaminobenzoic acid and dihydroxybenzoic acid, are not mammalian metabolites. Bacteria needing substances not available in host tissues should be unable to grow there and so be non-virulent. Transposon-generated deletion and deletion-inversion mutations at aroA caused loss of mouse virulence in Salmonella typhimurium; e.g., LD50, intraperitoneal route, increased from less than 10 to greater than 10(6), and LD50 by feeding increased from ca. 10(5) to greater than 10(8). Furthermore, a single injection of 10(5) live aro- bacteria protected mice of a Salmonella-susceptible line, BALB/c, against challenge, 4 weeks later, with 5 X 10(5) virulent S. typhimurium (i.e., greater than 10(4) LD50); a single dose of the live-vaccine strain given i.p. also protected against challenge one month later by feeding 2 X 10(7) of a virulent strain. Mice vaccinated by feeding 2 X 10(8) live aro- bacteria were unaffected by feeding, one month later, 2 X 10(7) of a virulent S. typhimurium strain ( = ca 100 LD50). Intravenous injection of microparticulate silica did not reduce the mouse i.p. LD50 of an aro- strain, and 3 i.p. injections of cyclophosphamide, 4 mgm, caused only a small reduction. Thus the reduced virulence of the aro- strain does much depend on the integrity of host cellular defense mechanisms. Non-reverting aro- derivatives made from proven calf-virulent S. typhimurium and S. dublin strains are being tested at the School of Veterinary Medicine, University of California at Davis. None of 26 calves given aro- live-vaccine bacteria intramuscularly (usually 10(9)) and none of 8 calves fed ca. 10(11) live aro- bacteria, died or became seriously ill. Vaccinated and control calves were challenged by feeding 10(11) bacteria of a virulent strain, S. typhimurium or S. dublin. This challenge caused death of 14 of 16 non-vaccinated calves. The results, to date, in vaccinated animals indicate that one aro- strain of each of the two Salmonella species is effective if given as a live vaccine in two intramuscular doses.
常见芳香族生物合成（aro）途径中的一个阻断环节使得大肠杆菌、沙门氏菌等对芳香族代谢物有严格需求；其中的对氨基苯甲酸和二羟基苯甲酸这两种物质并非哺乳动物的代谢产物。需要宿主组织中不存在的物质的细菌应该无法在那里生长，因此也就没有致病性。转座子引发的aroA基因缺失和缺失 - 倒位突变导致鼠伤寒沙门氏菌对小鼠的毒力丧失；例如，腹腔注射途径的半数致死剂量（LD50）从小于10增加到大于10⁶，经口投喂的LD50从约10⁵增加到大于10⁸。此外，单次注射10⁵个aro⁻细菌可保护易感沙门氏菌的BALB/c系小鼠，使其在4周后免受5×10⁵个有毒力的鼠伤寒沙门氏菌（即大于10⁴ LD50）的攻击；腹腔注射单剂量的活疫苗菌株也能保护小鼠在1个月后免受经口投喂2×10⁷个有毒力菌株的攻击。经口投喂2×10⁸个aro⁻细菌进行免疫的小鼠在1个月后经口投喂2×10⁷个有毒力的鼠伤寒沙门氏菌菌株（约等于100 LD50）时未受影响。静脉注射微粒二氧化硅并未降低aro⁻菌株对小鼠的腹腔注射LD50，3次腹腔注射4毫克环磷酰胺仅使其略有降低。因此，aro⁻菌株毒力的降低很大程度上依赖于宿主细胞防御机制的完整性。由已证实对小牛有毒力的鼠伤寒沙门氏菌和都柏林沙门氏菌菌株制备的非回复性aro⁻衍生物正在加利福尼亚大学戴维斯分校兽医学院进行测试。26头肌肉注射aro⁻活疫苗细菌（通常为10⁹个）的小牛以及8头经口投喂约10¹¹个aro⁻活细菌的小牛均未死亡或患重病。给接种疫苗的小牛和对照小牛经口投喂10¹¹个有毒力菌株（鼠伤寒沙门氏菌或都柏林沙门氏菌）的细菌进行攻击。这种攻击导致16头未接种疫苗的小牛中有14头死亡。迄今为止，在接种疫苗的动物身上得到的结果表明，两种沙门氏菌中的每种各有一个aro⁻菌株作为活疫苗分两次肌肉注射时是有效的。
