A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine.
A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine.
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土拉弗朗西斯菌 SCHU S4 菌株的突变体缺乏表达 58 千道尔顿蛋白质的能力，其毒力减弱，是一种有效的活疫苗。
DOI：
10.1128/iai.73.12.8345-8352.2005
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发表时间：
2005
影响因子：
3.1
通讯作者：
Sjöstedt,Anders
中科院分区：
文献类型：
--
作者：
Twine,Susan;Byström,Mona;Chen,Wangxue;Forsman,Mats;Golovliov,Igor;Johansson,Anders;Kelly,John;Lindgren,Helena;Svensson,Kerstin;Zingmark,Carl;Conlan,Wayne;Sjöstedt,Anders
土拉热弗朗西丝氏菌土拉热亚种（A型）菌株SCHU S4是对人类和其它哺乳动物具有高度毒性的病原体的原型菌株。其皮内（i.d.）小鼠的半数致死量（LD_（50））<10 CFU。我们发现了一个自发突变体，命名为FSC 043，具有i.d. LD_（50）>108CFU。FSC 043能有效地免疫小鼠抵抗A型强毒株的攻击，其保护效果至少与F. tularensisLVS是一种经验减毒的菌株，已被用作有效的人疫苗。使用比较蛋白质组学来鉴定在LVS和FSC 043中鉴定为缺陷的两种未知功能的蛋白质，并为两种编码基因中的每一种创建SCHU S4的缺失突变体。一个突变体Δ FTT 0918菌株不能表达58-kDa蛋白，具有i.d. LD_（50）为105 CFU，在小鼠腹腔巨噬细胞中的生长能力低于SCH_（S4）。从Δ FTT 0918突变体亚致死感染中恢复的小鼠在2个月后用>100 LD 50的高毒力A型菌株FSC 033攻击时存活。这是首次报道F.土拉热菌土拉热亚种及其作为活疫苗的用途。
Francisella tularensissubsp.tularensis(type A) strain SCHU S4 is a prototypic strain of the pathogen that is highly virulent for humans and other mammals. Its intradermal (i.d.) 50% lethal dose (LD50) for mice is <10 CFU. We discovered a spontaneous mutant, designated FSC043, of SCHU S4 with an i.d. LD50of >108CFU. FSC043 effectively vaccinated mice against challenge with a highly virulent type A strain, and the protective efficacy was at least as good as that ofF. tularensisLVS, an empirically attenuated strain which has been used as an efficacious human vaccine. Comparative proteomics was used to identify two proteins of unknown function that were identified as defective in LVS and FSC043, and deletion mutants of SCHU S4 were created for each of the two encoding genes. One mutant, the ΔFTT0918 strain, failed to express a 58-kDa protein, had an i.d. LD50of ∼105CFU, and was found to be less capable than SCHU S4 of growing in peritoneal mouse macrophages. Mice that recovered from sublethal infection with the ΔFTT0918 mutant survived when challenged 2 months later with >100 LD50s of the highly virulent type A strain FSC033. This is the first report of the generation of defined mutants ofF. tularensissubsp.tularensisand their use as live vaccines.