Dutkiewicz Jacek, Zając Violetta, Sroka Jacek, Wasiński Bernard, Cisak Ewa, Sawczyn Anna, Kloc Anna, Wójcik-Fatla Angelina
Department of Health Biohazards and Parasitology, Institute of Rural Health, Lublin, Poland.
Department of Hygiene of Food of Animal Origin, National Veterinary Research Institute, Puławy, Poland.
Ann Agric Environ Med. 2018 Mar 14;25(1):186-203. doi: 10.26444/aaem/85651. Epub 2018 Mar 2.
is a re-emerging zoonotic pathogen that may cause severe disease, mostly meningitis, in pigs and in humans having occupational contact with pigs and pork, such as farmers, slaughterhose workers and butchers. The first stage of the pathogenic process, similar in pigs and humans, is adherence to and colonisation of mucosal and/or epithelial surface(s) of the host. The second stage is invasion into deeper tissue and extracellular translocation of bacterium in the bloodstream, either free in circulation or attached to the surface of monocytes. If present in blood fails to cause fatal septicaemia, it is able to progress into the third stage comprising penetration into host's organs, mostly by crossing the blood-brain barrier and/or blood-cerebrospinal fluid barrier to gain access to the central nervous system (CNS) and cause meningitis. The fourth stage is inflammation that plays a key role in the pathogen esis of both systemic and CNS infections caused by . The pathogen may induce the overproduction of pro-inflammatory cytokines that cause septic shock and/or the recruitment and activation of different leukocyte populations, causing acute inflammation of the CNS. can also evoke - through activation of microglial cells, astrocytes and possibly other cell types - a fulminant inflammatory reaction of the brain which leads to intracranial complications, including brain oedema, increased intracranial pressure, cerebrovascular insults, and deafness, as a result of cochlear sepsis. In all stages of the pathogenic process, interacts with many types of immunocompetent host's cells, such as polymorphonuclear leukocytes, mononuclear macrophages, lymphocytes, dendritic cells and microglia, using a range of versatile virulence factors for evasion of the innate and adaptive immune defence of the host, and for overcoming environmental stress. It is estimated that produces more than 100 different virulence factors that could be classified into 4 groups: surface components or secreted elements, enzymes, transcription factors or regulatory systems and transporter factors or secretion systems. A major virulence factor is capsular polysaccharide (CPS) that protects bacteria from phagocytosis. However, it hampers adhesion to and invasion of host's cells, release of inflammatory cytokines and formation of the resistant biofilm which, in many cases, is vital for the persistence of bacteria. It has been demonstrated that the arising by mutation unencapsulated clones, which are more successful in penetration to and propagation within the host's cells, may coexist in the organism of a single host together with those that are encapsulated. Both 'complementary' clones assist each other in the successful colonization of host's tissues and persistence therein. has an open pan-genome characterized by a frequent gene transfer and a large diversity. Of the genetic determinants of pathogenicity, the most important are pathogenicity islands (PAI), in particular, a novel DNA segment of 89 kb length with evident pathogenic traits that has been designated as 89K PAI. It has been estimated that more than one-third of the virulence factors is associated with this PAI. It has been proved that the virulent strains possess smaller genomes, compared to avirulent ones, but more genes associated with virulence. Overall, the evolution of the species most probably aims towards increased pathogenicity, and hence the most significant task of the current research is an elaboration of a vaccine, efficient both for humans and pigs.
是一种再度出现的人畜共患病原体,可在猪以及与猪和猪肉有职业接触的人类(如农民、屠宰场工人和屠夫)中引起严重疾病,主要是脑膜炎。致病过程的第一阶段,在猪和人类中相似,是对宿主黏膜和/或上皮表面的黏附和定植。第二阶段是侵入更深层组织以及细菌在血流中的细胞外转运,细菌可游离于循环中或附着于单核细胞表面。如果血液中的细菌未能导致致命性败血症,它能够进入第三阶段,即主要通过穿越血脑屏障和/或血脑脊液屏障进入宿主器官,从而进入中枢神经系统(CNS)并引起脑膜炎。第四阶段是炎症,其在由该病原体引起的全身感染和中枢神经系统感染的发病机制中起关键作用。该病原体可诱导促炎细胞因子的过度产生,导致感染性休克和/或不同白细胞群体的募集和激活,引起中枢神经系统的急性炎症。它还可通过激活小胶质细胞、星形胶质细胞以及可能的其他细胞类型,引发脑部的暴发性炎症反应,导致颅内并发症,包括脑水肿、颅内压升高、脑血管损伤以及由于耳蜗败血症导致的耳聋。在致病过程的所有阶段,该病原体利用一系列多样的毒力因子与多种具有免疫活性的宿主细胞相互作用,如多形核白细胞、单核巨噬细胞、淋巴细胞、树突状细胞和小胶质细胞,以逃避宿主的固有免疫和适应性免疫防御,并克服环境压力。据估计,该病原体产生超过100种不同的毒力因子,可分为4组:表面成分或分泌元件、酶、转录因子或调节系统以及转运因子或分泌系统。一种主要的毒力因子是荚膜多糖(CPS),它可保护细菌免受吞噬作用。然而,它会阻碍对宿主细胞的黏附和侵入、炎性细胞因子的释放以及抗性生物膜的形成,而在许多情况下,抗性生物膜对于细菌的持续存在至关重要。已经证明,通过突变产生的无荚膜克隆在穿透宿主细胞并在其中繁殖方面更成功,它们可能与有荚膜的克隆共同存在于单个宿主的机体中。这两种“互补”克隆在宿主组织的成功定植及其在其中的持续存在方面相互协助。该病原体具有开放的泛基因组,其特征是频繁的基因转移和高度的多样性。在该病原体致病性的遗传决定因素中,最重要的是致病岛(PAI),特别是一个长度为89 kb的具有明显致病特征的新型DNA片段,已被命名为89K PAI。据估计,超过三分之一的该病原体毒力因子与这个PAI相关。已经证明,与无毒力菌株相比,有毒力的该病原体菌株基因组较小,但与毒力相关的基因更多。总体而言,该物种的进化很可能旨在增强致病性,因此当前研究的最重要任务是研制一种对人类和猪都有效的疫苗。