Uridinediphosphogalactose-4-epimerase deficiency in Salmonella typhimurium and its correction by plasmoid-borne galactose genes of Escherichia coli K-12: effects on mouse virulence, phagocytosis, and serum sensitivity.
The synthesis of smooth lipopolysaccharide (LPS) in relation to mouse virulence and resistance to serum bactericidal activity in vitro and to rapid intravenous clearance in vivo was studied in Salmonella typhimurium by using a virulent [median lethal dose (LD(50)) = 10(2)], smooth, and genetically marked strain, a uridinediphosphogalactose epimerase-deficient mutant of it which was, therefore, rough, and a derivative of the mutant made smooth again by acquisition of the galactose-positive genes of Escherichia coli. The mutant was of reduced virulence (LD(50) = 10(6)) but the smooth derivative regained the virulence character typical of the parent. The non-smooth phenotype also made the mutant, but not the smooth relatives (parent and derivative), susceptible to serum bactericidal activity and also to rapid intravenous clearance by phagocytosis by the liver. The mutant was similarly treated by germ-free mice (expected to be relatively free of opsonizing antibodies). The clearance of the mutant could be impaired by prior intravenous inoculation of homologous bacteria or their LPS but was reversible by preopsonization of the second inoculum with nonimmune mouse serum, suggesting that the initial inoculum preempted the opsonizing antibodies. Independent evidence of clearance specificity was also provided in mixed inoculum experiments on impaired mice by the rapid clearance of an antigenically unrelated heptose-deficient mutant while maintaining the decelerated clearance of the epimerase mutant. The latter, however, was converted to accelerated clearance by the intravenous inoculation during the impaired state of anti-epimerase mutant immune mouse serum.
D000818:Animals; D001770:Blood Bactericidal Activity; D002238:Carbohydrate Epimerases; D002417:Cattle / Q000276:immunology; D002470:Cell Survival; D004926:Escherichia coli / Q000201:enzymology*; D005111:Extrachromosomal Inheritance; D005690:Galactose; D005947:Glucose; D007106:Immune Sera; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000302:isolation & purification; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D009154:Mutation; D009895:Opsonin Proteins; D010587:Phagocytosis; D010641:Phenotype; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000302:isolation & purification; D012486:Salmonella typhimurium / Q000201:enzymology*; D014539:Uridine Diphosphate Sugars; D014774:Virulence
D007106:Immune Sera; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; D014539:Uridine Diphosphate Sugars; D002238:Carbohydrate Epimerases; D005947:Glucose; D005690:Galactose