The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge.
The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge.
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DOI：
10.1080/21505594.2020.1804275
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发表时间：
2020-12
期刊：
影响因子：
5.2
通讯作者：
Lafontaine ER
中科院分区：
文献类型：
--
作者：
Dyke JS;Huertas-Diaz MC;Michel F;Holladay NE;Hogan RJ;He B;Lafontaine ER
鼻疽伯克霍尔德氏菌是一种高致病性细菌，导致致命的人畜共患病鼻疽。该生物体指定了多种膜蛋白，这些膜蛋白代表了在宿主-病原体界面处的位置的对策发展的主要目标。我们研究了其中一种蛋白质，即β-淀粉样蛋白，发现它与B的能力有关。鼻疽抵抗补体介导的杀伤并在体外在宿主细胞内复制，在体内表达并在感染过程中诱导抗体，并在气溶胶感染的小鼠模型中促成毒力。B的pal基因突变。发现鼻疽野生型菌株ATCC 23344特别减毒，因为用相当于5，350 LD 50的剂量攻击的BALB/c小鼠完全清除了感染。基于这些发现，我们检验了一个假设，即含有α-淀粉样蛋白的疫苗能增强对气溶胶攻击的保护性免疫。为了实现这一点，将pal基因克隆到疫苗载体副流感病毒5（PIV 5）中，并用致死剂量的B感染用该病毒免疫的小鼠。鼻疽这些实验表明，单剂量的表达HIV的PIV 5在攻击后40天内提供80%的存活率。相比之下，用PIV 5对照病毒构建体接种的小鼠只有10%在感染后存活。综上所述，我们的数据确定肽聚糖相关脂蛋白ε是B的关键毒力决定因子。鼻疽是鼻疽疫苗的有效靶点。
Burkholderia mallei is a highly pathogenic bacterium that causes the fatal zoonosis glanders. The organism specifies multiple membrane proteins, which represent prime targets for the development of countermeasures given their location at the host-pathogen interface. We investigated one of these proteins, Pal, and discovered that it is involved in the ability of B. mallei to resist complement-mediated killing and replicate inside host cells in vitro, is expressed in vivo and induces antibodies during the course of infection, and contributes to virulence in a mouse model of aerosol infection. A mutant in the pal gene of the B. mallei wild-type strain ATCC 23344 was found to be especially attenuated, as BALB/c mice challenged with the equivalent of 5,350 LD50 completely cleared infection. Based on these findings, we tested the hypothesis that a vaccine containing the Pal protein elicits protective immunity against aerosol challenge. To achieve this, the pal gene was cloned in the vaccine vector Parainfluenza Virus 5 (PIV5) and mice immunized with the virus were infected with a lethal dose of B. mallei. These experiments revealed that a single dose of PIV5 expressing Pal provided 80% survival over a period of 40 days post-challenge. In contrast, only 10% of mice vaccinated with a PIV5 control virus construct survived infection. Taken together, our data establish that the Peptidoglycan-associated lipoprotein Pal is a critical virulence determinant of B. mallei and effective target for developing a glanders vaccine.
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影响因子：
3.1
作者：
Bullard, B;Lipski, SL;Lafontaine, ER
通讯作者：
Lafontaine, ER
DOI：
10.1164/ajrccm.165.7.2109009
发表时间：
2002-04-01
影响因子：
24.7
作者：
Abe, Y;Murphy, TF;Thanavala, YM
通讯作者：
Thanavala, YM
影响因子：
--
作者：
Duche, Denis;Houot, Laetitia
通讯作者：
Houot, Laetitia
影响因子：
2.8
作者：
Dubuisson, JF;Vianney, A;Lazzaroni, JC
通讯作者：
Lazzaroni, JC
影响因子：
3.1
作者：
GREEN, BA;VAZQUEZ, ME;DOYLE, WJ
通讯作者：
DOYLE, WJ