文献类型：期刊文献

英文题名：Iron-Regulated Lysis of Recombinant Escherichia coli in Host Releases Protective Antigen and Confers Biological Containment

作者：Guan, Lingyu[1];Mu, Wei[1];Champeimont, Jonathan[2];Wang, Qiyao[1];Wu, Haizhen[1];Xiao, Jingfan[1];Lubitz, Werner[2];Zhang, Yuanxing[1];Liu, Qin[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Univ Vienna, Dept Med Pharmaceut Chem, A-1090 Vienna, Austria

年份：2011

卷号：79

期号：7

起止页码：2608

外文期刊名：INFECTION AND IMMUNITY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000291788700011)】；

基金：This work was supported by the joint project National Natural Science Foundation of China-Austrian Science Fund (30811130545).

语种：英文

摘要：The use of a recombinant bacterial vector vaccine is an attractive vaccination strategy to induce an immune response to a carried protective antigen. The superiorities of live bacterial vectors include mimicry of a natural infection, intrinsic adjuvant properties, and the potential for administration by mucosal routes. Escherichia coli is a simple and efficient vector system for production of exogenous proteins. In addition, many strains are nonpathogenic and avirulent, making it a good candidate for use in recombinant vaccine design. In this study, we screened 23 different iron-regulated promoters in an E. coli BL21(DE3) vector and found one, P-viuB, with characteristics suitable for our use. We fused P-viuB with lysis gene E, establishing an in vivo inducible lysis circuit. The resulting in vivo lysis circuit was introduced into a strain also carrying an IPTG (isopropyl-beta-D-thiogalactopyranoside)-inducible P-T7-controlled protein synthesis circuit, forming a novel E. coli-based protein delivery system. The recombinant E. coli produced a large amount of antigen in vitro and could deliver the antigen into zebrafish after vaccination via injection. The strain subsequently lysed in response to the iron-limiting signal in vivo, implementing antigen release and biological containment. The gapA gene, encoding the protective antigen GAPDH (glyceraldehyde-3-phosphate dehydrogenase) from the fish pathogen Aeromonas hydrophila LSA34, was introduced into the E. coli-based protein delivery system, and the resultant recombinant vector vaccine was evaluated in turbot (Scophtalmus maximus). Over 80% of the vaccinated fish survived challenge with A. hydrophila LSA34, suggesting that the E. coli-based antigen delivery system has great potential in bacterial vector vaccine applications.