Factors responsible for increased susceptibility of mice to intestinal colonization after treatment with streptomycin

Abstract

Streptomycin sulfate (5 mg/ml) was added to the drinking water of Swiss white mice. After treatment for 1 week, the mice were challenged orogastrically with 10(8) Pseudomonas aeruginosa cells. The organism failed to multiply in the intestinal tract of either treated or untreated animals, but could be recovered from contents and tissues after 48 h. In a previous study, Salmonella typhimurium was shown to multiply in the intestines of streptomycin-treated but not untreated mice when 10(3) organisms were used as inoculum. Streptomycin administration had little effect on Eh, protein or carbohydrate concentrations of cecal contents, or intestinal motility. However, it caused a statistically significant increase in water content and pH of contents and a decrease in the concentrations of acetic, propionic, butyric, and valeric acids. S. typhimurium multiplied in pooled cecal contents obtained from both streptomycin-treated and untreated animals, but its multiplication rate and total populations were significantly greater in contents from treated animals. P. aeruginosa did not multiply in contents from either treated or untreated mice. Similar results were obtained when the organisms were inoculated into nutrient broth adjusted to simulate the pH levels and volatile fatty acid (VFA) concentrations in cecal contents of treated and untreated mice. The addition of brain heart infusion broth to cecal contents from untreated animals, in concentrations that support multiplication of S. typhimurium and P. aeruginosa, did not reverse inhibition. The addition of VFA to cecal contents from treated animals to equal the concentration in cecal contents from untreated animals caused inhibition of a magnitude observed in cecal contents from untreated animals. The results indicate that VFA operating at the pH level of cecal contents of conventional mice inhibit the multiplication of both S. typhimurium and P. aeruginosa and restrict colonization of the intestine by these organisms. The decrease in VFA concentrations that occurs as a result of streptomycin administration adequately explains the increased susceptibility of treated mice to colonization with S. typhimurium. It does not explain the increased susceptibility of treated mice to P. aeruginosa colonization, however.

Colonization resistance and microbial ecophysiology: using gnotobiotic mouse models and single-cell technology to explore the intestinal jungle

“…General candidate inhibitors include short-chain fatty acids (SCFA), bile salts, H 2 S as well as bacteriocins (Savage, 1977;Freter et al, 1983b). Decreased CR has frequently been correlated with reduced intestinal SCFA concentrations, that is, in antibiotic-treated or germfree mice (Hoverstad et al, 1986;Que et al, 1986). Further, in mice, a dysbiotic C. difficile 'supershedder' state is characterized by a reduction in butyrate and acetate and an increase in succinate levels (Lawley et al, 2012).…”

Acute colonization study of polychlorinated biphenyl‐degrading pseudomonads in the mouse intestinal tract: Comparison of single and multiple exposures

“…Strain BC17 can be enumerated from an intestinal homogenate for up to 24 h. Reingestion of strains BC6 and BC17 was obviously much less than of the other dosed P. aeruginosa strains studied. Que et al [23] reported that a clinical P. aeruginosa isolate was recover-able from mouse intestines 48 h after dosing orogastrically. In our single exposure model, mice were housed in metabolism cages on wire floors, which minimized coprophagy.…”

“…Several interrelated factors have been shown to be responsible for the exclusion of "foreign" microorganisms from the intestines. The production of inhibitory agents such as volatile fatty acids is responsible for the inhibition of S. typhimurium [23] and C. difficile [28]. These same substances have an inhibitory effect on P. aeruginosa [23].…”

“…The production of inhibitory agents such as volatile fatty acids is responsible for the inhibition of S. typhimurium [23] and C. difficile [28]. These same substances have an inhibitory effect on P. aeruginosa [23]. Hydrogen sulfide production has also been associated with colonization inhibition in the (3.1. tract due to effective competition for nutrient utilization under high H2S conditions [26].…”

“…Hydrogen sulfide production has also been associated with colonization inhibition in the (3.1. tract due to effective competition for nutrient utilization under high H2S conditions [26]. The pH and oxidation-reduction potential of the intestinal tract also are responsible for excluding bacterial species [23,29,30]. The competition for adhesion sites excludes some organisms [31,32].…”