志贺氏菌属的致病因子及其菌苗研究进展

Genetic Determinant of Shigella Pathogenicity and Strategies for Development of Potential Candidate Vaccines

痢疾是一种在全世界范围内流行的传染病,由志贺氏菌属引起。志贺氏菌有4个种群:福氏志贺氏菌、宋内氏志贺氏菌、痢疾志贺氏菌和鲍氏志贺氏菌。除宋内氏菌以外,每个种群还有不同的血清型。 迄今已知志贺氏菌的主要致病因子有:位于志贺氏菌大质粒上与侵袭力相关的基因,其功能是使志贺氏菌能进入人的肠上皮细胞;位于志贺氏菌染色体上的脂多糖基因,其功能与已进入宿主细胞的志贺氏菌的增殖相关;志贺氏毒素,它是由Ⅰ型痢疾志贺氏菌产生,其基因也位于染色体上,它具有肠毒、细胞毒和神经毒作用;此外,志贺氏菌对铁的吸收能力和温度也是志贺氏菌毒力的调节因子。 痢疾菌苗的研制始于本世纪40年代,起初从胃肠道外途径用死菌苗对志愿者进行了现场试验,结果表明死菌苗没有明显的保护作用。后来采用口服途径、但口服死菌苗对人体也没有保护作用,而口服减毒活菌苗有保护作用。但这些菌苗减毒的遗传背景不清楚,存在回复突变的可能性。现已构建了毒力基因缺失的减毒株,这种减毒株不可能发生回复突变成有毒株,很有希望成为理想的痢疾菌苗候选株。

Shigellosis caused by Shigella speciesis endemic throughout the world. The Shigella genusincludes four species: Shigella flexineri S. sonnei,S. dysenteriae and S. boydii. On the basis of theantigenicity of the O - specific polysaccharide chain ofthe lipopolysaccharide molecule of the cell envelope,they can be further divided into different serotypesexcept S sonnei. The genetic determinants of Shigella pathogenicityfound so far include: the genes in the large plasmid ofShigella species coded for the ability to invade humanintestinal epithelium cells; the genes in chromosome en-coding for lipopolysaccharide which is essential for bacte-rial multiplication after penetratron into the epithelialcells; Shiga toxin produced by S. dysenteriae serotype I,which possesses enterotoxicity, neurotoxicity, and cytotoxi-city; temperature is also used by Shigella as positiveregulative factor of virulence; besides, the ability of Shigella to compete for iron is also considered as avirulence factor. During the 1940s inactivated whole - cell prepa-rations were used parentefally in volunteer or in fieldtrials, but no protection was recorded. Then inacti-vated whole cells were orally administered, but alsono protection was seen. In the early 1960s it wasfound that a spontaneously arising avirulent mutant ofS. flexineri 2a was to be safe and effective when used asan oral live vaccine. However there is possibility of re-version to virulence because the attenuated genetic back-ground is unclear. At present a series of deleted mutantsof virulence factors have been constructed. It is surprisedthat these strains could be used as ideal vaccines againstShigella species, because they could not reversed to viru-lence.