巴氏链球菌,漏报的机会病原体,被认为是全世界许多动物和人类脑膜炎和菌血症的日益公认的原因。然而,除了一些流行病学研究,没有关于基因缺失诱变的报道,毒力因子,该病原体的水库生态位或动物感染模型。在这项研究中,我们首先从新断奶的仔猪脑中分离出一株巴氏链球菌。该猪分离株WUSP067的基因组序列与两个人菌株的基因组序列具有高度同源性。基因组比较分析表明,菌株WUSP067含有人类菌株中不存在的岩藻糖利用簇,它与来自猪链球菌的整合和共轭元件(ICE)ICEssuZJ20091101-2具有91%的同一性,另一种重要的猪细菌病原体。菌株WUSP067对红霉素具有抗性,泰拉霉素,林可霉素,克林霉素,多西环素和庆大霉素,和ICE是携带抗菌素耐药基因的载体。使用3周龄新断奶的ICR小鼠建立感染模型。菌株WUSP067的50%致死剂量值为每只小鼠4.0×107集落形成单位。受感染的小鼠表现出严重的脑膜炎迹象和大脑的病理变化。此外,胶囊缺陷型突变体是使用自然转化产生的,我们证明了胶囊是巴氏链球菌必需的毒力因子。此外,我们发现健康猪的扁桃体和肺门淋巴结可能是这种细菌的贮库。因此,我们的研究提供了有关巴氏链球菌的致病特征和耐药性的有价值的信息,并为研究其发病机制铺平了道路。
Streptococcus pasteurianus, an underreported opportunistic pathogen, is considered an increasingly recognized cause of meningitis and bacteremia in many animals and humans worldwide. However, except for some epidemiological studies, there is no report about the gene-deletion mutagenesis, virulence factors, reservoir niches or animal infection models for this pathogen. In this study, we first isolated an S. pasteurianus strain from a newly weaned piglet\'s brain with meningitis. The genomic sequence of this swine isolate WUSP067 shared high homology with that of two human strains. The comparative genome analysis showed that strain WUSP067 contained a fucose utilization cluster absent in human strains, and it shared 91% identity with that of an integrative and conjugative element (ICE) ICEssuZJ20091101-2 from Streptococcus suis, another important swine bacterial pathogen. Strain WUSP067 was resistant to erythromycin, tulathromycin, lincomycin, clindamycin, doxycycline and gentamycin, and ICEs are vehicles for harbouring antimicrobial resistance genes. The infection model was established using the 3-week-old newly weaned ICR mice. The 50% lethal dose value of strain WUSP067 was 4.0 × 107 colony-forming units per mouse. The infected mice showed severe signs of meningitis and pathological changes in brains. Furthermore, the capsule-deficient mutant was generated using natural transformation, and we showed that capsule was an essential virulence factor for S. pasteurianus. In addition, we found that tonsils and hilar lymph nodes of healthy pigs may be reservoir niches for this bacterium. Thus, our study provided valuable information about the pathogenetic characteristics and antimicrobial resistance of S. pasteurianus and paved the way for studying its pathogenesis.