Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney.
Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney.
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DOI：
10.3389/fcimb.2022.926994
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
钩端螺旋体病的分子和细胞发病机制仍然知之甚少。基于比较细菌基因组学数据，我们最近确定了假设的PF 07598基因家族编码分泌外毒素（VM蛋白），介导体外细胞毒性。为了解决VM蛋白是否介导体内钩端螺旋体病的发病机制，我们测试了VM蛋白免疫小鼠将保护免受致死性攻击感染并减少关键靶器官中的细菌负荷的假设。用重组E.大肠杆菌产生的、无内毒素的钩端螺旋体VM蛋白（来源于L.问号血清型Lai）与人相容性佐剂吡喃葡萄糖苷脂质A/角鲨烯水包油的组合。接受全长重组VM蛋白的小鼠被保护免于L.犬型问号血清型，肝脏和肾脏中的细菌负荷减少3-4 log 10。这些实验表明，用重组VM蛋白免疫可预防钩端螺旋体病的临床发病机制，并导致该动物模型中关键靶器官感染显著减少。这些数据支持钩端螺旋体VM蛋白作为毒力因子的作用，并表明VM蛋白为基础的，血清型独立的泛钩端螺旋体病疫苗可能是可行的。
The molecular and cellular pathogenesis of leptospirosis remains poorly understood. Based on comparative bacterial genomics data, we recently identified the hypothetical PF07598 gene family as encoding secreted exotoxins (VM proteins) that mediate cytotoxicity in vitro. To address whether VM proteins mediate in vivo leptospirosis pathogenesis, we tested the hypothesis that VM protein immunization of mice would protect against lethal challenge infection and reduce bacterial load in key target organs. C3H/HeJ mice were immunized with recombinant E. coli-produced, endotoxin-free, leptospiral VM proteins (derived from L. interrogans serovar Lai) in combination with the human-compatible adjuvant, glucopyranoside lipid A/squalene oil-in-water. Mice receiving full length recombinant VM proteins were protected from lethal challenge infection by L. interrogans serovar Canicola and had a 3-4 log10 reduction in bacterial load in the liver and kidney. These experiments show that immunization with recombinant VM proteins prevents leptospirosis clinical pathogenesis and leads to markedly reduced key target organ infection in this animal model. These data support the role of leptospiral VM proteins as virulence factors and suggest the possibility that a VM protein-based, serovar-independent, pan-leptospirosis vaccine may be feasible.
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DOI：
10.4103/ijmr.ijmr_1022_16
发表时间：
2018-01
期刊：
The Indian journal of medical research
影响因子：
--
作者：
Bashiru G;Bahaman AR
通讯作者：
Bahaman AR
影响因子：
25.7
作者：
Fouts, Derrick E.;Torralba, Manolito;Nelson, Karen E.;Brenner, David A.;Schnabl, Bernd
通讯作者：
Schnabl, Bernd
影响因子：
1.8
作者：
Bouvet, J.;Lemaitre, L.;Guigal, P. M.
通讯作者：
Guigal, P. M.
影响因子：
3.8
作者：
Coutinho ML;Choy HA;Kelley MM;Matsunaga J;Babbitt JT;Lewis MS;Aleixo JA;Haake DA
通讯作者：
Haake DA
影响因子：
--
作者：
Grassmann, Andre A.;Felix, Samuel R.;Dellagostin, Odir A.
通讯作者：
Dellagostin, Odir A.