qseC及luxS双基因缺失对多杀性巴氏杆菌毒力及其交叉免疫保护性的影响

Effects of dual-deletion of qseC and luxS gene on virulence and cross-protection in Pasteurella multocida

qseC和luxS是多杀性巴氏杆菌群体感应系统相关基因,为探讨其双缺失对多杀性巴氏杆菌致病性及交叉免疫保护的影响,本研究在前期构建的牛源A型多杀性巴氏杆菌CQ2株(PmCQ2)qseC基因缺失株(ΔqseC)的基础上进行了luxS基因缺失,构建了qseC及luxS双基因缺失株(ΔqseCΔluxS)。与野生型PmCQ2相比,该双基因缺失株在生物膜产生方面显著上升,而其荚膜生成量、血清敏感性及其毒力却显著下调,与qseC单基因缺失相比,双基因缺失在调节菌株部分生物学特性方面具有正向或负向叠加效应。疫苗交叉免疫保护性方面,与ΔqseC及野生型PmCQ2比较发现,双基因缺失株中luxS基因的缺失,减弱了部分qseC基因缺失所赋予菌株的交叉免疫保护效果,但却增强了菌株对牛源F型多杀性巴氏杆菌的交叉免疫保护作用,相比PmCQ2的无交叉免疫保护作用,qseC及luxS双基因缺失仍赋予了菌株很好的交叉免疫保护性。研究结果表明,群体感应基因qseC和luxS均可调控多杀性巴氏杆菌毒力及其交叉免疫保护性,该双基因缺失株可作为多杀性巴氏杆菌广谱型疫苗候选菌株。

qseC and luxS gene are belong to quorum-sensing related genes in Pasteurella multocida,and the effects of qseC and LuxS dual-deletion on virulence and cross-protection in Pymultocida are still not well understood.In present study,the mutant of dual-deletion of qseC and luxS gene(ΔqseCΔwxS)was constructed based on qseC mutant(ΔgseC)derived from bovine P.multocida type A CQ2(PmCQ2).Compared with wild type PmCQ2,dual deleting of qseC and luxS gene promotes the mutant production of biofilm,and downregulates the mutant in capsule production,serum sensitivity and virulence.Compared with single qseC gene deletion,the dual deletion of qseC and luxS gene has positive or negative superimposition effects in some biological properties such as the production of biofilm and capsule.In terms of vaccine cross-protection,compared withΔqseC and wild-type PmCQ2,the deletion of luxS gene inΔqseCΔluxS weakened the cross-protection effect brought by qseC gene deletion,but increased the cross-protection effect with qseC gene deletion against bovine P.multocida serotype F.Compared with wild type PmCQ2 vaccine,the dual deletion of qseC and luxS gene still endowed the mutant good cross-protection against P.multocida infection.The results indicated that both qseC and luxS could regulate the virulence and cross-protection of P.multocida,and qseC and luxS gene mutant can be used as a candidate vaccine against P.multocida strains of multiple serotypes infection.