Treatment of E. coli and klebsiella bacteremia in agranulocytic animals with antiserum to a UDP-gal epimerase-deficient mutant.
Treatment of E. coli and klebsiella bacteremia in agranulocytic animals with antiserum to a UDP-gal epimerase-deficient mutant.
复制标题
用针对 UDP-gal 差向异构酶缺陷突变体的抗血清治疗无粒细胞动物中的大肠杆菌和克雷伯氏菌菌血症。
DOI：
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发表时间：
1973
影响因子：
4.4
通讯作者：
Abraham I. Braude
中科院分区：
文献类型：
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作者：
Elizabeth J. Ziegler;Herndon Douglas;James E. Sherman;Charles E. Davis;Abraham I. Braude
为了生产对不同革兰氏阴性细菌具有广泛保护作用的抗血清，我们用大肠杆菌 O111 的 UDP 半乳糖缺陷突变体 (J5) 对兔子进行免疫接种，该突变体不受 O 抗原的阻碍，因为它不能将半乳糖掺入核心 LPS。由于没有 O 侧链，核心可用于产生针对具有相似核心的多种细菌的抗血清。此类抗血清先前已被证明可以防止不相关的内毒素产生皮肤反应和全身性施瓦茨曼反应以及死亡。目前的研究报告了用这种抗血清治疗菌血症的结果。
用氮芥使兔子粒细胞减少，并喂食肺炎克雷伯菌、大肠杆菌 O17（多重抗生素耐药性）或大肠杆菌 O4，从而产生菌血症。由于大多数兔子体内不含大肠菌群，因此这些微生物在肠道内定植，当粒细胞消失时，就会出现大量菌血症。当这三种生物体出现菌血症时静脉注射非免疫血清时，只有 3.1% 至 5.7% 的存活率。相比之下，给予 J5 突变体抗血清的动物存活率分别为 33.3%（来自大肠杆菌 O4）、40%（来自克雷伯氏菌）和 69.2%（来自多重抗生素耐药性大肠杆菌 O17）（组合 p < 0.0005）。针对亲本大肠杆菌 O111 的抗血清（O 抗原完整）没有提供显着的保护作用。 J5 抗血清对大肠杆菌 O17 的死亡保护作用大于庆大霉素 (50%)，庆大霉素是该菌株唯一敏感的抗生素。给予 J5 抗血清的兔子比给予非免疫血清的兔子更快地清除标记的细菌。 J5突变体的抗血清被认为可以通过充当抗毒素和调理素来预防无关的革兰氏阴性菌引起的致命菌血症。
In order to produce antiserum with broad protection against different Gramnegative bacteria we immunized rabbits with a UDP-galactose-deficient mutant (J5) of Escherichia coli O111 that is unencumbered by O antigen since it cannot incorporate galactose into core LPS. Without O side chains, core is accessible for producing antiserum to a wide range of bacteria with similar cores. Such antiserum has previously been shown to prevent unrelated endotoxins from producing dermal and generalized Shwartzman reactions, and death. The current study reports the results of treating bacteremia with this antiserum.
Bacteremia was produced in rabbits made granulocytopenic with nitrogen mustard and fed either Klebsiella pneumoniae, E. coli O17 (multiply antibiotic-resistant), or E. coli O4. Since most rabbits are coliform-free, the organisms colonized the gut and overwhelming bacteremia occurred as granulocytes disappeared. When nonimmune serum was given intravenously (i.v.) at the onset of bacteremia with any of these three organisms, only 3.1% to 5.7% survived. In contrast, survival rates in animals given antiserum to the J5 mutant were 33.3% from E. coli O4, 40% from Klebsiella, and 69.2% from the multiply antibiotic-resistant E. coli O17 (combined p < 0.0005). Antiserum to the parent E. coli O111, (with O antigen intact) provided no significant protection. The protection against death from E. coli O17 by J5 antiserum was greater than that obtained from gentamicin (50%), the only antibiotic to which this strain was sensitive. Rabbits given J5 antiserum cleared labeled bacteria more rapidly than those given nonimmune sera. Antiserum to the J5 mutant is thought to prevent lethal bacteremia from unrelated Gram-negative bacteria by acting as both antitoxin and opsonin.