Key Laboratory of Applied Technology On Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal, Health Big Data Analytics, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A & F University, 666 Wusu Street, Hangzhou, 311300, China.
Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
Vet Res. 2023 Feb 27;54(1):15. doi: 10.1186/s13567-023-01142-4.
Attenuated Salmonella Typhimurium is a promising antigen delivery system for live vaccines such as polysaccharides. The length of polysaccharides is a well-known key factor in modulating the immune response induced by glycoconjugates. However, the relationship between the length of Lipopolysaccharide (LPS) O-antigen (OAg) and the immunogenicity of S. Typhimurium remains unclear. In this study, we assessed the effect of OAg length determined by wzz on Salmonella colonization, cell membrane permeability, antimicrobial activity, and immunogenicity by comparing the S. Typhimurium wild-type ATCC14028 strain to those with various OAg lengths of the Δwzz mutant and Δwzz::wzz. The analysis of the OAg length distribution revealed that, except for the very long OAg, the short OAg length of 2-7 repeat units (RUs) was obtained from the Δwzz mutant, the intermediate OAg length of 13-21 RUs was gained from Δwzz::wzz, and the long OAg length of over 20 RUs was gained from the wild-type. In addition, we found that the OAg length affected Salmonella colonization, cell permeability, and antibiotic resistance. Immunization of mice revealed that shortening the OAg length by altering wzz had an effect on serum bactericidal ability, complement deposition, and humoral immune response. S. Typhimurium mutant strain Δwzz::wzz possessed good immunogenicity and was the optimum option for delivering E. coli O2 O-polysaccharides. Furthermore, the attenuated strain ATCC14028 ΔasdΔcrpΔcyaΔrfbPΔwzz::wzz-delivered E. coli O2 OAg gene cluster outperforms the ATCC14028 ΔasdΔcrpΔcyaΔrfbP in terms of IgG eliciting, cytokine expression, and immune protection in chickens. This study sheds light on the role of OAg length in Salmonella characteristics, which may have a potential application in optimizing the efficacy of delivered polysaccharide vaccines.
减毒鼠伤寒沙门氏菌是一种有前途的抗原传递系统，可用于多糖等活疫苗。多糖的长度是调节糖缀合物诱导的免疫反应的已知关键因素。然而，脂多糖 (LPS) O-抗原 (OAg) 的长度与鼠伤寒沙门氏菌的免疫原性之间的关系尚不清楚。在这项研究中，我们通过比较鼠伤寒沙门氏菌野生型 ATCC14028 菌株与具有不同 OAg 长度的 Δwzz 突变体和 Δwzz::wzz 菌株，评估了由 wzz 决定的 OAg 长度对沙门氏菌定植、细胞膜通透性、抗菌活性和免疫原性的影响。OAg 长度分布的分析表明，除了非常长的 OAg 外，Δwzz 突变体获得了 2-7 个重复单位 (RU) 的短 OAg 长度，Δwzz::wzz 获得了 13-21 RU 的中间 OAg 长度，而野生型获得了超过 20 RU 的长 OAg 长度。此外，我们发现 OAg 长度影响沙门氏菌定植、细胞通透性和抗生素耐药性。对小鼠的免疫接种表明，通过改变 wzz 来缩短 OAg 长度会影响血清杀菌能力、补体沉积和体液免疫反应。鼠伤寒沙门氏菌突变株 Δwzz::wzz 具有良好的免疫原性，是递送大肠杆菌 O2 O-多糖的最佳选择。此外，减毒菌株 ATCC14028ΔasdΔcrpΔcyaΔrfbPΔwzz::wzz 递送的大肠杆菌 O2 OAg 基因簇在诱导 IgG、细胞因子表达和鸡免疫保护方面优于 ATCC14028ΔasdΔcrpΔcyaΔrfbP。这项研究揭示了 OAg 长度在沙门氏菌特性中的作用，这可能在优化递送多糖疫苗的疗效方面具有潜在应用。
