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Attenuated Francisella novicida transposon mutants protect mice against wild-type challenge.减毒的新凶手弗朗西斯菌转座子突变体可保护小鼠免受野生型菌株的攻击。
Infect Immun. 2006 Sep;74(9):5095-105. doi: 10.1128/IAI.00598-06.
2
Characterization of Francisella tularensis Schu S4 defined mutants as live-attenuated vaccine candidates.将土拉弗朗西斯菌Schu S4特定突变体鉴定为减毒活疫苗候选株。
Pathog Dis. 2015 Aug;73(6):ftv036. doi: 10.1093/femspd/ftv036. Epub 2015 May 17.
3
A Francisella tularensis subspecies novicida purF mutant, but not a purA mutant, induces protective immunity to tularemia in mice.土拉热弗朗西斯菌新凶手亚种purF突变株而非purA突变株可诱导小鼠对土拉菌病产生保护性免疫。
Vaccine. 2007 Mar 1;25(11):2011-8. doi: 10.1016/j.vaccine.2006.11.054. Epub 2006 Dec 8.
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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.土拉弗朗西斯菌菌株SCHU S4的一个缺乏表达一种58千道尔顿蛋白质能力的突变体，其毒力减弱，是一种有效的活疫苗。
Infect Immun. 2005 Dec;73(12):8345-52. doi: 10.1128/IAI.73.12.8345-8352.2005.
5
Vaccination with a defined Francisella tularensis subsp. novicida pathogenicity island mutant (DeltaiglB) induces protective immunity against homotypic and heterotypic challenge.用特定的土拉弗朗西斯菌新凶手亚种致病岛突变体（ΔiglB）进行疫苗接种可诱导针对同型和异型攻击的保护性免疫。
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BALB/c mice, but not C57BL/6 mice immunized with a ΔclpB mutant of Francisella tularensis subspecies tularensis are protected against respiratory challenge with wild-type bacteria: association of protection with post-vaccination and post-challenge immune responses.BALB/c 小鼠，但不是用弗朗西斯氏菌属土拉弗朗西斯菌亚种的 ΔclpB 突变体免疫的 C57BL/6 小鼠，可免受野生型细菌的呼吸道挑战：保护与接种后和接种后免疫反应有关。
Vaccine. 2012 May 21;30(24):3634-45. doi: 10.1016/j.vaccine.2012.03.036. Epub 2012 Apr 3.
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Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent subsp. .减毒活土拉弗朗西丝菌疫苗对呼吸道感染强毒. 亚种的保护作用。
Front Cell Infect Microbiol. 2018 May 15;8:154. doi: 10.3389/fcimb.2018.00154. eCollection 2018.
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Characterization of Schu S4 mutants as live attenuated tularemia vaccine candidates.鉴定苏 S4 突变株作为减毒活鼠疫疫苗候选株。
Virulence. 2020 Dec;11(1):283-294. doi: 10.1080/21505594.2020.1746557.
9
Differential ability of novel attenuated targeted deletion mutants of Francisella tularensis subspecies tularensis strain SCHU S4 to protect mice against aerosol challenge with virulent bacteria: effects of host background and route of immunization.新型减毒靶向缺失突变株弗朗西斯氏菌亚种土拉弗朗西斯菌 SCHU S4 对小鼠气溶胶攻毒的保护作用不同：宿主背景和免疫途径的影响。
Vaccine. 2010 Feb 17;28(7):1824-31. doi: 10.1016/j.vaccine.2009.12.001. Epub 2009 Dec 16.
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Inhalation of Francisella novicida Delta mglA causes replicative infection that elicits innate and adaptive responses but is not protective against invasive pneumonic tularemia.吸入新凶手弗朗西斯菌ΔmglA会引发复制性感染，该感染会引发先天性和适应性反应，但对侵袭性肺型兔热病没有保护作用。
Microbes Infect. 2008 Jun;10(7):773-80. doi: 10.1016/j.micinf.2008.04.008. Epub 2008 Apr 22.

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The pentose phosphate pathway constitutes a major metabolic hub in pathogenic Francisella.戊糖磷酸途径是病原弗朗西斯菌的主要代谢枢纽。
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Sequence Determinants Spanning -10 Motif and Spacer Region Implicated in Unique Sigma 32-Dependent Promoter Activity of Gene.跨越-10基序和间隔区的序列决定因素与基因独特的依赖σ32启动子活性有关。
Front Microbiol. 2019 Aug 2;10:1772. doi: 10.3389/fmicb.2019.01772. eCollection 2019.
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Front Cell Infect Microbiol. 2018 May 15;8:154. doi: 10.3389/fcimb.2018.00154. eCollection 2018.
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Transcription Elongation Factor GreA Plays a Key Role in Cellular Invasion and Virulence of Francisella tularensis subsp. novicida.转录延伸因子 GreA 在土拉弗朗西斯菌亚种 novicida 的细胞侵袭和毒力中发挥关键作用。
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Differential Growth of , Which Alters Expression of Virulence Factors, Dominant Antigens, and Surface-Carbohydrate Synthases, Governs the Apparent Virulence of SchuS4 to Immunized Animals.……的差异生长改变了毒力因子、主要抗原和表面碳水化合物合酶的表达，决定了SchuS4对免疫动物的表观毒力。 （注：原文中“Differential Growth of ”后面缺少具体内容）
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本文引用的文献

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Studies on tularemia; observations on tularemia in normal and vaccinated monkeys.兔热病研究；正常及接种疫苗猴的兔热病观察
J Immunol. 1948 Feb;58(2):183-202.
2
Direct repeat-mediated deletion of a type IV pilin gene results in major virulence attenuation of Francisella tularensis.IV型菌毛基因的直接重复介导缺失导致土拉弗朗西斯菌的主要毒力减弱。
Mol Microbiol. 2006 Mar;59(6):1818-30. doi: 10.1111/j.1365-2958.2006.05061.x.
3
Intranasal vaccination with a defined attenuated Francisella novicida strain induces gamma interferon-dependent antibody-mediated protection against tularemia.用特定减毒的新凶手弗朗西斯菌菌株进行鼻内接种可诱导γ干扰素依赖性抗体介导的兔热病保护作用。
Infect Immun. 2006 Apr;74(4):2063-71. doi: 10.1128/IAI.74.4.2063-2071.2006.
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AEROSOL INFECTION OF MAN WITH PASTEURELLA TULARENSIS.人通过气溶胶感染土拉弗朗西斯菌。
Bacteriol Rev. 1961 Sep;25(3):262-7. doi: 10.1128/br.25.3.262-267.1961.
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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.土拉弗朗西斯菌菌株SCHU S4的一个缺乏表达一种58千道尔顿蛋白质能力的突变体，其毒力减弱，是一种有效的活疫苗。
Infect Immun. 2005 Dec;73(12):8345-52. doi: 10.1128/IAI.73.12.8345-8352.2005.
6
Identification of new secreted effectors in Salmonella enterica serovar Typhimurium.肠炎沙门氏菌鼠伤寒血清型中新分泌效应蛋白的鉴定。
Infect Immun. 2005 Oct;73(10):6260-71. doi: 10.1128/IAI.73.10.6260-6271.2005.
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Tularemia vaccine: past, present and future.兔热病疫苗：过去、现在与未来。
Antonie Van Leeuwenhoek. 2005 May;87(4):277-81. doi: 10.1007/s10482-004-6251-7.
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Vaccination strategies for Francisella tularensis.土拉弗朗西斯菌的疫苗接种策略。
Adv Drug Deliv Rev. 2005 Jun 17;57(9):1403-14. doi: 10.1016/j.addr.2005.01.030.
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Intranasal vaccination induces protective immunity against intranasal infection with virulent Francisella tularensis biovar A.鼻内接种可诱导针对强毒土拉弗朗西斯菌生物变种A鼻内感染的保护性免疫。
Infect Immun. 2005 May;73(5):2644-54. doi: 10.1128/IAI.73.5.2644-2654.2005.
10
Efficacy of the live attenuated Francisella tularensis vaccine (LVS) in a murine model of disease.减毒活土拉弗朗西斯菌疫苗（LVS）在小鼠疾病模型中的疗效。
Vaccine. 2005 Apr 8;23(20):2680-6. doi: 10.1016/j.vaccine.2004.03.071.

减毒的新凶手弗朗西斯菌转座子突变体可保护小鼠免受野生型菌株的攻击。

Attenuated Francisella novicida transposon mutants protect mice against wild-type challenge.

作者信息

Tempel Rebecca, Lai Xin-He, Crosa Lidia, Kozlowicz Briana, Heffron Fred

机构信息

6543 Basic Sciences Addition/CROET Building, Department of Molecular Microbiology and Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.

出版信息

Infect Immun. 2006 Sep;74(9):5095-105. doi: 10.1128/IAI.00598-06.

DOI:10.1128/IAI.00598-06
PMID:16926401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1594869/
Abstract

Francisella tularensis is the bacterial pathogen that causes tularemia in humans and a number of animals. To date, there is no approved vaccine for this widespread and life-threatening disease. The goal of this study was to identify F. tularensis mutants that can be used in the development of a live attenuated vaccine. We screened F. novicida transposon mutants to identify mutants that exhibited reduced growth in mouse macrophages, as these cells are the preferred host cells of Francisella and an essential component of the innate immune system. This approach yielded 16 F. novicida mutants that were 100-fold more attenuated for virulence in a mouse model than the wild-type parental strain. These mutants were then tested to determine their abilities to protect mice against challenge with high doses of wild-type bacteria. Five of the 16 attenuated mutants (with mutations corresponding to dsbB, FTT0742, pdpB, fumA, and carB in the F. tularensis SCHU S4 strain) provided mice with protection against challenge with high doses (>8 x 10(5) CFU) of wild-type F. novicida. We believe that these findings will be of use in the design of a vaccine against tularemia.

摘要

土拉弗朗西斯菌是一种可导致人类和多种动物患兔热病的细菌病原体。迄今为止，针对这种广泛传播且危及生命的疾病尚无获批疫苗。本研究的目标是鉴定可用于开发减毒活疫苗的土拉弗朗西斯菌突变体。我们筛选了新凶手弗朗西斯菌转座子突变体，以鉴定那些在小鼠巨噬细胞中生长减缓的突变体，因为这些细胞是弗朗西斯菌的首选宿主细胞，也是先天免疫系统的重要组成部分。这种方法产生了16个新凶手弗朗西斯菌突变体，它们在小鼠模型中的毒力比野生型亲本菌株减弱了100倍。然后对这些突变体进行测试，以确定它们保护小鼠免受高剂量野生型细菌攻击的能力。16个减毒突变体中的5个（其突变对应于土拉弗朗西斯菌SCHU S4菌株中的dsbB、FTT0742、pdpB、fumA和carB）为小鼠提供了针对高剂量（>8×10⁵CFU）野生型新凶手弗朗西斯菌攻击的保护作用。我们相信这些发现将有助于设计一种抗兔热病疫苗。