Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan, Hubei 430079, China.
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan, Hubei 430079, China.
Gene. 2022 Oct 20;841:146771. doi: 10.1016/j.gene.2022.146771. Epub 2022 Jul 26.
Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia, which is a severe and often fatal disease that results in significant economic loss. The means by which A. pleuropneumoniae survives within the host are not clear. High temperature requirement A (HtrA) proteases have been shown to affect cell viability during stressful conditions and are virulence factors in many bacterial species. In this study, we examined the biological role of HtrA during A. pleuropneumoniae infection by analyzing the impact of htrA mutation on virulence-associated phenotypes. We found that htrA mutation had a dramatic impact on stress tolerance. The htrA mutant (ΔhtrA) displayed a lethal phenotype at elevated temperature (42 °C). Further, ΔhtrA exhibited increased susceptibility to HO-induced oxidative stress when compared to the parental strain (SLW01) and a complementation strain (ΔhtrA-Compl). Animal infection assays demonstrated that absence of HtrA led to decreased in vivo colonization ability, and ΔhtrA is less virulent in pigs relative to SLW01. Furthermore, pig competitive infection assays demonstrated fewer blood associated CFUs with ΔhtrA infection than with SLW01. These results demonstrate HtrA plays a significant role in the survival and growth of A. pleuropneumoniae during stressful conditions, and that immune escape and invasiveness are important to the process of A. pleuropneumoniae infection.
胸膜肺炎放线杆菌是猪传染性胸膜肺炎的病原体，该病是一种严重且常致命的疾病，会导致重大的经济损失。目前仍不清楚胸膜肺炎放线杆菌在宿主体内的生存方式。已有研究表明，高温需求 A （HtrA）蛋白酶在应激条件下影响细胞活力，并且是许多细菌物种的毒力因子。在这项研究中，我们通过分析 htrA 突变对与毒力相关表型的影响，研究了 HtrA 在胸膜肺炎放线杆菌感染过程中的生物学作用。结果发现，htrA 突变对胁迫耐受有显著影响。与亲本株（SLW01）和互补株（ΔhtrA-Compl）相比，htrA 突变株（ΔhtrA）在高温（42°C）下表现出致命表型。此外，与 SLW01 相比，ΔhtrA 对 HO 诱导的氧化应激更敏感。动物感染实验表明，HtrA 的缺失导致体内定植能力下降，与 SLW01 相比，ΔhtrA 在猪体内的毒力降低。此外，猪竞争性感染实验表明，ΔhtrA 感染时血液相关 CFU 数少于 SLW01。这些结果表明，HtrA 在胸膜肺炎放线杆菌应激条件下的生存和生长中发挥重要作用，免疫逃避和侵袭性对于胸膜肺炎放线杆菌感染过程很重要。
