Identification of genes contributing to the virulence of Francisella tularensis SCHU S4 in a mouse intradermal infection model.
Identification of genes contributing to the virulence of Francisella tularensis SCHU S4 in a mouse intradermal infection model.
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DOI：
10.1371/journal.pone.0005463
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Sjöstedt A
中科院分区：
文献类型：
--
作者：
Kadzhaev K;Zingmark C;Golovliov I;Bolanowski M;Shen H;Conlan W;Sjöstedt A
图拉氏方济氏菌是一种高度毒力的人类病原体。毒力最强的菌株属于图拉氏亚种，这些菌株有时会引起一种致命的疾病。尽管最近进行了密集的研究工作，但解释图拉氏亚种菌株的独特特征、将它们与其他图拉氏杆菌菌株区分开来以及解释它们的高毒力的信息非常有限。在这里，我们报告了使用定向突变来研究各种基因或途径在菌株Schu S4毒力中的作用，Schu S4是图拉山亚种的模式菌株。通过观察皮内注射不同剂量细菌后的感染结果来评估Schu S4突变体的毒力。通过这种途径，Schu S4株的LD50为1 CFU。对20个框内缺失突变体和37个转座子突变体进行了毒力测定。大多数突变体没有表现出延长死亡时间的现象，其中特别是ΔpyrB和ΔrecA。在其余的6个独特靶点中，tolC、rep、FTT0609、FTT1149c、ahpC和Hfq的突变导致死亡时间显著延长，而rplA、wbtI、iglB、iglD、Purl、PurF、GGT、kdtA和glpX 9个靶点的突变导致显著衰减，LD50为103 cfu。事实上，后7个突变体表现出非常显著的衰减，其LD_(50)为≥107cfu。结果表明，靶标突变体的特征获得了关于基本毒力决定因素的重要信息，这将有助于鉴定迄今鲜为人知的图拉氏丝孢子菌亚种图拉氏杆菌的极端毒力。
Francisella tularensis is a highly virulent human pathogen. The most virulent strains belong to subspecies tularensis and these strains cause a sometimes fatal disease. Despite an intense recent research effort, there is very limited information available that explains the unique features of subspecies tularensis strains that distinguish them from other F. tularensis strains and that explain their high virulence. Here we report the use of targeted mutagenesis to investigate the roles of various genes or pathways for the virulence of strain SCHU S4, the type strain of subspecies tularensis. The virulence of SCHU S4 mutants was assessed by following the outcome of infection after intradermal administration of graded doses of bacteria. By this route, the LD50 of the SCHU S4 strain is one CFU. The virulence of 20 in-frame deletion mutants and 37 transposon mutants was assessed. A majority of the mutants did not show increased prolonged time to death, among them notably ΔpyrB and ΔrecA. Of the remaining, mutations in six unique targets, tolC, rep, FTT0609, FTT1149c, ahpC, and hfq resulted in significantly prolonged time to death and mutations in nine targets, rplA, wbtI, iglB, iglD, purL, purF, ggt, kdtA, and glpX, led to marked attenuation with an LD50 of >103 CFU. In fact, the latter seven mutants showed very marked attenuation with an LD50 of ≥107 CFU. The results demonstrate that the characterization of targeted mutants yielded important information about essential virulence determinants that will help to identify the so far little understood extreme virulence of F. tularensis subspecies tularensis.
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DOI：
10.1007/bf02464894
发表时间：
1989-06-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
KANG, WK;ICHO, T;ISONO, K
通讯作者：
ISONO, K
影响因子：
3.1
作者：
Golovliov, I;Baranov, V;Sjöstedt, A
通讯作者：
Sjöstedt, A
DOI：
10.1196/annals.1409.012
发表时间：
2007-01-01
期刊：
FRANCISELLA TULARENSIS: BIOLOGY, PATHOGENICITY, EPIDEMIOLOGY, AND BIODEFENSE
影响因子：
--
作者：
Conlan, J. Wayne;Oyston, Petra C. F.
通讯作者：
Oyston, Petra C. F.
DOI：
10.1196/annals.1409.014
发表时间：
2007-01-01
期刊：
FRANCISELLA TULARENSIS: BIOLOGY, PATHOGENICITY, EPIDEMIOLOGY, AND BIODEFENSE
影响因子：
--
作者：
Elkins, Karen L.;Cowley, Siobhan C.;Bosio, Catharine M.
通讯作者：
Bosio, Catharine M.
DOI：
10.1073/pnas.0602582103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Gil, Horacio;Platz, Gabrielle J.;Thanassi, David G.
通讯作者：
Thanassi, David G.