Twine Susan M, Vinogradov Evguenii, Lindgren Helena, Sjostedt Anders, Conlan J Wayne
National Research Council Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, ON K1A 1L1, Canada.
Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå SE-90185, Sweden.
Pathogens. 2012 Sep 10;1(1):12-29. doi: 10.3390/pathogens1010012.
Using a strategy of gene deletion mutagenesis, we have examined the roles of genes putatively involved in lipopolysaccharide biosynthesis in the virulent facultative intracellular bacterial pathogen, subspecies , strain SCHU S4 in LPS biosynthesis, protein glycosylation, virulence and immunogenicity. One mutant, , did not elaborate a long chain -polysaccharide (OPS), was completely avirulent for mice, and failed to induce a protective immune response against challenge with wild type bacteria. Another mutant, , produced a long chain OPS with altered chemical and electrophoretic characteristics. This mutant showed markedly reduced glycosylation of several known glycoproteins. Additionally this mutant was highly attenuated, and elicited a protective immune response against systemic, but not respiratory challenge with wild type SCHU S4. A third mutant, , produced an unconjugated long chain OPS, lacking a detectable core structure, and which was not obviously expressed at the surface. It was avirulent and elicited partial protection against systemic challenge only.
通过基因缺失诱变策略,我们研究了在有毒兼性胞内细菌病原体——亚种菌株SCHU S4中,假定参与脂多糖生物合成的基因在脂多糖生物合成、蛋白质糖基化、毒力和免疫原性方面的作用。一个突变体,不产生长链多糖(OPS),对小鼠完全无毒,并且未能诱导针对野生型细菌攻击的保护性免疫反应。另一个突变体产生了具有改变的化学和电泳特性的长链OPS。该突变体显示几种已知糖蛋白的糖基化明显减少。此外,该突变体高度减毒,并引发了针对野生型SCHU S4全身攻击而非呼吸道攻击的保护性免疫反应。第三个突变体产生了一种未结合的长链OPS,缺乏可检测的核心结构,并且在表面未明显表达。它无毒,仅对全身攻击引发部分保护作用。