The effect of O-antigen length determinant wzz on the immunogenicity of Salmonella Typhimurium for Escherichia coli O2 O-polysaccharides delivery

Abstract

AbstractAttenuatedSalmonellaTyphimurium 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 ofS. Typhimurium remains unclear. In this study, we assessed the effect of OAg length determined bywzzSTonSalmonellacolonization, cell membrane permeability, antimicrobial activity, and immunogenicity by comparing theS. Typhimurium wild-type ATCC14028 strain to those with various OAg lengths of the ΔwzzSTmutant and ΔwzzST::wzzECO2. 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 ΔwzzSTmutant, the intermediate OAg length of 13–21 RUs was gained from ΔwzzST::wzzECO2, and the long OAg length of over 20 RUs was gained from the wild-type. In addition, we found that the OAg length affectedSalmonellacolonization, cell permeability, and antibiotic resistance. Immunization of mice revealed that shortening the OAg length by alteringwzzSThad an effect on serum bactericidal ability, complement deposition, and humoral immune response.S. Typhimurium mutant strain ΔwzzST::wzzECO2possessed good immunogenicity and was the optimum option for deliveringE. coliO2 O-polysaccharides. Furthermore, the attenuated strain ATCC14028 ΔasdΔcrpΔcyaΔrfbPΔwzzST::wzzECO2-deliveredE. coliO2 OAg gene cluster outperforms the ATCC14028 ΔasdΔcrpΔcyaΔrfbPin terms of IgG eliciting, cytokine expression, and immune protection in chickens. This study sheds light on the role of OAg length inSalmonellacharacteristics, which may have a potential application in optimizing the efficacy of delivered polysaccharide vaccines.