College of Veterinary Medicine, Southwest University, Chongqing, 400715, China.
Department of Environment and Safety Engineering, Taiyuan institute of technology, Taiyuan, 030008, China.
BMC Vet Res. 2024 Mar 9;20(1):94. doi: 10.1186/s12917-024-03948-6.
Pasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At present, there is still no effective commercial vaccine against PmA infection. In this study, a mutant strain (PmCQ2Δ4555-4580) with brand-new phenotypes was obtained after serially passaging at 42 °C. Whole genome resequencing and PCR analysis showed that PmCQ2Δ4555-4580 missed six genes, including PmCQ2_004555, PmCQ2_004560, PmCQ2_004565, PmCQ2_004570, PmCQ2_004575, and PmCQ2_004580. Importantly, the virulence of PmCQ2Δ4555-4580 was reduced by approximately 2.8 × 10 times in mice. Notably, live PmCQ2Δ4555-4580 could provide 100%, 100% and 40% protection against PmA, PmB and PmF, respectively; and inactivated PmCQ2Δ4555-4580 could provide 100% and 87.5% protection against PmA and PmB. Interestingly, immune protection-related proteins were significantly upregulated in PmCQ2Δ4555-4580 based on RNA-seq and bioinformatics analysis. Meaningfully, by in vitro expression, purification and in vivo immunization, 12 proteins had different degrees of immune protective effects. Among them, PmCQ2_008205, PmCQ2_010435, PmCQ2_008190, and PmCQ2_004170 had the best protective effect, the protection rates against PmA were 50%, 40%, 30%, and 30%, respectively, and the protective rates against PmB were 62.5%, 42.9%, 37.5%, and 28.6%, respectively. Collectively, PmCQ2Δ4555-4580 is a potential vaccine candidate for the prevention of Pasteurellosis involving in high expression of immune protective related proteins.
多杀性巴氏杆菌 A 型（PmA）主要引起牛的呼吸道疾病，如肺炎，给养殖业造成了巨大的经济损失。目前，针对 PmA 感染还没有有效的商业疫苗。本研究通过在 42°C 下连续传代，获得了一株具有全新表型的突变株（PmCQ2Δ4555-4580）。全基因组重测序和 PCR 分析表明，PmCQ2Δ4555-4580 缺失了 6 个基因，包括 PmCQ2_004555、PmCQ2_004560、PmCQ2_004565、PmCQ2_004570、PmCQ2_004575 和 PmCQ2_004580。重要的是，PmCQ2Δ4555-4580 在小鼠体内的毒力降低了约 2.8×10 倍。值得注意的是，活的 PmCQ2Δ4555-4580 对 PmA、PmB 和 PmF 的保护率分别为 100%、100%和 40%；而灭活的 PmCQ2Δ4555-4580 对 PmA 和 PmB 的保护率分别为 100%和 87.5%。有趣的是，基于 RNA-seq 和生物信息学分析，PmCQ2Δ4555-4580 中与免疫保护相关的蛋白显著上调。有意义的是，通过体外表达、纯化和体内免疫，12 种蛋白具有不同程度的免疫保护作用。其中，PmCQ2_008205、PmCQ2_010435、PmCQ2_008190 和 PmCQ2_004170 具有最佳的保护效果，对 PmA 的保护率分别为 50%、40%、30%和 30%，对 PmB 的保护率分别为 62.5%、42.9%、37.5%和 28.6%。综上所述，PmCQ2Δ4555-4580 是一种具有高表达免疫保护相关蛋白的潜在疫苗候选株，可用于预防巴氏杆菌病。
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