Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Shanghai, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, People's Republic of China.
Vet Res. 2018 Sep 17;49(1):93. doi: 10.1186/s13567-018-0589-8.
In this study, the Riemerella anatipestifer mutant strain RA1062 was obtained by screening a random Tn4351 transposon mutant library. The mutant strain was unreactive with the anti-CH3 lipopolysaccharide monoclonal antibody, as demonstrated with an enzyme-linked immunosorbent assay, and its M949_RS01035 gene was inactivated. When cultured in trypticase soy broth, the late stage growth of the mutant RA1062 was significantly decreased. The mutant RA1062 was stained with crystal violet and presented a rough lipopolysaccharide phenotype, which differed from that of the wild-type strain CH3, suggesting that deletion of the M949_RS01035 gene resulted in defective lipopolysaccharide. Silver staining and Western blot analyses further confirmed that the RA1062 lipopolysaccharide had a deficiency in ladder-like binding pattern, as compared to lipopolysaccharide of the wild-type CH3 strain. In addition, the mutant RA1062 showed a higher susceptibility to complement-dependent killing, increased bacterial adhesion and invasion capacities to Vero cells, decreased blood bacterial loads, and attenuated virulence in infected ducks, when compared to the wild-type strain CH3. Moreover, RNA-Seq and real-time polymerase chain reaction analyses indicated that two genes were up-regulated and two were down-regulated in the mutant RA1062 genome. Furthermore, an animal protection experiment showed that immunization of ducks with inactivated RA1062 bacterin conferred effective cross-protection against challenge with the virulent R. anatipestifer serotypes 1, 2, and 10. This study presents evidence that the M949_RS01035 gene is involved in bacterial phenotype, virulence, and gene regulation in R. anatipestifer. The mutant strain RA1062 could be used as a cross-protective vaccine candidate.
在这项研究中,通过筛选随机 Tn4351 转座子突变体文库,获得了减毒的鸭疫里默氏杆菌突变株 RA1062。该突变株与抗 CH3 脂多糖单克隆抗体无反应,酶联免疫吸附试验(ELISA)证实其 M949_RS01035 基因失活。在胰蛋白胨大豆肉汤中培养时,突变株 RA1062 的后期生长明显减少。突变株 RA1062 用结晶紫染色,呈现粗糙的脂多糖表型,与野生型 CH3 菌株不同,表明 M949_RS01035 基因缺失导致脂多糖缺陷。银染和 Western blot 分析进一步证实,与野生型 CH3 菌株的脂多糖相比,RA1062 脂多糖 ladder-like 结合模式缺失。此外,与野生型 CH3 菌株相比,突变株 RA1062 对补体依赖性杀伤更敏感,对 Vero 细胞的粘附和侵袭能力增强,血液细菌载量减少,对感染鸭的毒力减弱。此外,RNA-Seq 和实时聚合酶链反应(PCR)分析表明,突变株 RA1062 基因组中有两个基因上调,两个基因下调。进一步的动物保护实验表明,灭活 RA1062 菌苗免疫鸭子可有效交叉保护鸭疫里默氏杆菌 1、2 和 10 型强毒株的攻毒。本研究表明,M949_RS01035 基因参与了鸭疫里默氏杆菌的细菌表型、毒力和基因调控。突变株 RA1062 可作为交叉保护性疫苗候选株。