Relationship between cell death and altered lipid A synthesis in a temperature-sensitive lethal mutant of Salmonella typhimurium that is conditionally defective in 3-deoxy-D-manno-octulosonate-8-phosphate synthesis.
The relationship between the inability to synthesize a complete 3-deoxy-D-manno-octulosonate region of lipopolysaccharide and cell death was investigated in a temperature-sensitive lethal mutant of Salmonella typhimurium. The defect in lipopolysaccharide synthesis is due to a mutation in the structural gene for 3-deoxy-D-manno-octulosonate-8-phosphate synthetase (designated kdsA) and results in the synthesis of a temperature-sensitive enzyme. Expression of the kdsA lesion at elevated temperatures, at which the synthesis of 3-deoxy-D-manno-octulosonate is complete blocked, is required for expression of the temperature-sensitive lethal phenotype. However, the defect in lipopolysaccharide synthesis is not alone sufficient cause for the observed cell death. Genetic evidence if presented which indicates that the mutant possesses a second mutation, or possibly multiple mutations, whose lethal expression is dependent on the inability of the mutant to synthesize a fully acylated and 3-deoxy-D-manno-octulosonate-substituted lipid A portion of lipopolysaccharide at elevated temperatures.
D000446:Aldehyde-Lyases / Q000235:genetics; D005798:Genes, Bacterial; D008050:Lipid A / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D009154:Mutation; D010428:Pentosephosphates / Q000494:pharmacology; D010743:Phospholipids / Q000032:analysis; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D013403:Sugar Phosphates / Q000096:biosynthesis*; D013696:Temperature; D014161:Transduction, Genetic
C012875:3-deoxy-D-manno-octulosonic acid-8-dihydrogen phosphate; D008050:Lipid A; D008070:Lipopolysaccharides; D010428:Pentosephosphates; D010743:Phospholipids; D013403:Sugar Phosphates; C028055:arabinose 5-phosphate; C020011:2-dehydro-3-deoxyphosphooctonate aldolase; D000446:Aldehyde-Lyases