Wallis T S
Institute for Animal Health, Compton, Berkshire, UK.
Dev Biol (Basel). 2004;119:343-50.
The threat of zoonotic infection with food-poisoning enteric pathogens remains a major threat to public health throughout the world. Control of enteric pathogens within food-producing animals remains an obvious strategy to prevent the introduction of these pathogens into the human food chain. Vaccines are currently available for the control of Salmonella; however such vaccines vary in their efficacy and acceptability to the food production industries and consumers. Vaccines for the control of enterohaemorrhagic E. coli and Campylobacter are currently unavailable. Understanding the molecular basis of how these organisms colonise the intestines and cause disease is essential for the development of effective multivalent vaccines. The mechanisms by which these organisms colonise the gut will be reviewed. Bacterial Type Three Secretion Systems (TTSS) have been shown to be major virulence factors influencing the colonisation and pathogenicity of Salmonella and enterohaemorrhagic E. coli in some but not all animal species. Thus, understanding the specific nature of host/pathogen interactions is crucial in the development of cross-species vaccines. TTSSs act by delivering effector proteins into intestinal epithelial cells, which act to modify signalling events in host cells causing cytoskeletal and pathophysiological changes to the benefit of the pathogen. Disruption of TTSSs and/or related secreted effector proteins can be adopted as a strategy for the attenuation of live vaccine strains. Furthermore secreted effector proteins have the potential to be incorporated into sub-unit vaccines. As many of such effector proteins are conserved between different serotypes, such vaccines offer the hope of cross-serotype protective immune responses. Novel experimental vaccines are currently being developed to exploit these and other recent discoveries in bacterial virulence mechanisms. The potential of such vaccines to control zoonotic pathogens will be discussed.
食源性肠道致病菌的人畜共患病感染威胁仍然是全球公共卫生面临的主要威胁。控制食品生产动物体内的肠道致病菌仍然是防止这些病原体进入人类食物链的一项明显策略。目前已有用于控制沙门氏菌的疫苗;然而,此类疫苗在效力以及食品生产行业和消费者的接受度方面存在差异。目前尚无用于控制肠出血性大肠杆菌和弯曲杆菌的疫苗。了解这些生物体如何在肠道中定殖并引发疾病的分子基础对于开发有效的多价疫苗至关重要。本文将综述这些生物体在肠道中定殖的机制。细菌三型分泌系统(TTSS)已被证明是影响沙门氏菌和肠出血性大肠杆菌在部分(而非全部)动物物种中定殖和致病性的主要毒力因子。因此,了解宿主/病原体相互作用的具体性质对于开发跨物种疫苗至关重要。TTSS通过将效应蛋白递送到肠道上皮细胞中发挥作用,这些效应蛋白会改变宿主细胞中的信号传导事件,导致细胞骨架和病理生理变化,从而有利于病原体。破坏TTSS和/或相关的分泌效应蛋白可作为减毒活疫苗菌株的一种策略。此外,分泌的效应蛋白有潜力被纳入亚单位疫苗。由于许多此类效应蛋白在不同血清型之间是保守的,此类疫苗有望引发跨血清型的保护性免疫反应。目前正在开发新型实验性疫苗,以利用这些以及细菌毒力机制方面的其他最新发现。本文将讨论此类疫苗控制人畜共患病原体的潜力。