Yang Yang, Hu Pei, Gao Lixu, Yuan Xiang, Hardwidge Philip R, Li Tian, Li Pan, He Fang, Peng Yuanyi, Li Nengzhang
College of Veterinary Medicine, Southwest University, Chongqing, 400716, China.
College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Vet Res. 2021 Nov 20;52(1):140. doi: 10.1186/s13567-021-01009-6.
QseC, a histidine sensor kinase of the QseBC two-component system, acts as a global regulator of bacterial stress resistance, biofilm formation, and virulence. The function of QseC in some bacteria is well understood, but not in Pasteurella multocida. We found that deleting qseC in P. multocida serotype A:L3 significantly down-regulated bacterial virulence. The mutant had significantly reduced capsule production but increased resistance to oxidative stress and osmotic pressure. Deleting qseC led to a significant increase in qseB expression. Transcriptome sequencing analysis showed that 1245 genes were regulated by qseC, primarily those genes involved in capsule and LPS biosynthesis and export, biofilm formation, and iron uptake/utilization, as well as several immuno-protection related genes including ompA, ptfA, plpB, vacJ, and sodA. In addition to presenting strong immune protection against P. multocida serotypes A:L1 and A:L3 infection, live ΔqseC also exhibited protection against P. multocida serotype B:L2 and serotype F:L3 infection in a mouse model. The results indicate that QseC regulates capsular production and virulence in P. multocida. Furthermore, the qseC mutant can be used as an attenuated vaccine against P. multocida strains of multiple serotypes.
QseC是QseBC双组分系统中的一种组氨酸传感器激酶，作为细菌应激抗性、生物膜形成和毒力的全局调节因子。QseC在某些细菌中的功能已得到充分了解，但在多杀性巴氏杆菌中却并非如此。我们发现，在多杀性巴氏杆菌A:L3血清型中删除qseC会显著下调细菌毒力。该突变体的荚膜产量显著降低，但对氧化应激和渗透压的抗性增加。删除qseC导致qseB表达显著增加。转录组测序分析表明，有1245个基因受qseC调控，主要是那些参与荚膜和脂多糖生物合成与输出、生物膜形成以及铁摄取/利用的基因，以及几个与免疫保护相关的基因，包括ompA、ptfA、plpB、vacJ和sodA。除了对多杀性巴氏杆菌A:L1和A:L3血清型感染具有强大的免疫保护作用外，活的ΔqseC在小鼠模型中还对多杀性巴氏杆菌B:L2血清型和F:L3血清型感染表现出保护作用。结果表明，QseC调节多杀性巴氏杆菌的荚膜产生和毒力。此外，qseC突变体可作为针对多种血清型多杀性巴氏杆菌菌株的减毒疫苗。
