Peng Xiaowei, Liu Yufu, Qin Yuming, Jiang Hui, Feng Yu, Sun Jiali, Niu Kai, Gao Qiang, Dong Hao, Ding Jiabo
National Reference Laboratory for Animal Brucellosis, China Institute of Veterinary Drug Control, Beijing, China.
South China Agricultural University, Guangzhou, China.
Front Vet Sci. 2020 Jan 10;6:459. doi: 10.3389/fvets.2019.00459. eCollection 2019.
Brucellosis is one of the most common zoonotic epidemics with a serious threat to public health and livestock development in many countries across the world. Vaccination is a key control strategy toward preventing brucellosis in high-prevalence regions. Recently, a rough-type mutant strain (RM57) induced from a strain M1981 showed protective effects in guinea pigs indicating that it is a good vaccine candidate. In this study, stress response assays were performed to reveal the mechanisms underlying virulence attenuation of RM57. In addition, a genome-wide transcriptome profile of RM57 was analyzed relative to the parent strain M1981 in order to reveal genetic factors controlling the phenotypes. Our results indicated a similar sensitivity to various stress conditions in RM57 owing to a lack of significant differences from its parent strain. Transcriptome analysis showed that a total of 1,205 genes were differentially expressed between RM57 and M1981 with gene ontology terms revealing that these genes are involved in energy production and conversion, translation, ribosomal structure, and biogenesis. Pathway enrichment analysis revealed that genes involved in oxidative phosphorylation, ribosome, nitrogen metabolism, tyrosine metabolism, and two-component system were significantly affected. As a result of these differences at the molecular level, the function of type IV secretion system in RM57 was found to be affected leading to reduced virulence of the RM57 mutant strain in both macrophage and mice infection models.
布鲁氏菌病是最常见的人畜共患病之一，对世界上许多国家的公共卫生和畜牧业发展构成严重威胁。疫苗接种是在高流行地区预防布鲁氏菌病的关键控制策略。最近，从菌株M1981诱导产生的粗糙型突变株（RM57）在豚鼠中显示出保护作用，表明它是一种良好的疫苗候选株。在本研究中，进行了应激反应试验以揭示RM57毒力减弱的机制。此外，相对于亲本菌株M1981分析了RM57的全基因组转录组图谱，以揭示控制表型的遗传因素。我们的结果表明，RM57对各种应激条件的敏感性与亲本菌株相似，因为两者之间没有显著差异。转录组分析表明，RM57和M1981之间共有1205个基因差异表达，基因本体术语显示这些基因参与能量产生和转换、翻译、核糖体结构和生物发生。通路富集分析表明，参与氧化磷酸化、核糖体、氮代谢、酪氨酸代谢和双组分系统的基因受到显著影响。由于这些分子水平的差异，发现RM57中IV型分泌系统的功能受到影响，导致RM57突变株在巨噬细胞和小鼠感染模型中的毒力降低。
