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For study of the role of lipopolysaccharide (LPS) character in colonization of the mouse large intestine, use was made of S. typhimurium strain SL5316, which is streptomycin resistant and smooth (wild-type LPS) but nonvirulent because it is Aro- (aromatic dependent). Several rough variants of different LPS chemotype derived from strain SL5316 comprised: an rfb deletion transductant making type Ra (complete core) LPS; an rfaJ mutant making incomplete core of type Rb2; and an rfa-990 mutant making LPS core less complete than chemotype Rb2. We tested these strains for colon-colonizing ability by feeding them to male CD-1 mice receiving streptomycin sulfate (5 g/liter) in their drinking water. Each strain, if fed alone, was found in the feces throughout the 15 days of the experiment at about 108 CFU/g for the smooth strain or 107 CFU/g for each of its rough derivatives. However, when mice were fed equal numbers of two strains (with differentiating antibiotic resistance characters), the strain with the more complete LPS was found in the feces in great excess, 1000- to 100,000-fold, according to the pair. Thus, when strains were placed in direct competition with one another, their relevant colon-colonizing abilities were found to be wild type > rfb >> rfaJ > rfa-990, showing that the ability of a Salmonella strain to colonize the mouse large intestine decreases as its LPS structure becomes more defective.