Antibiotic residues and R-plasmid selection: are in vitro methods good models?

Abstract

Three clones of E. coli, one of which was harbouring a tetracycline resistance plasmid were inoculated together into the stomach of axenic mice. Without antibiotic selective pressure, the R-Plasmid bearing strain became dominant in the faeces of mice, while the R-plasmid free strain was eliminated. When the R-plasmid bearing strain was given to mice 4 days after the inoculation with the R-plasmid free strain, it was repressed and remained at the stable level of 10(4.5) organisms per g of faeces. But a rapid spread of the R-plasmid was observed, tetracycline resistant bacteria become dominant within one day, and replace the tetracycline sensitive E. coli. The tetracycline resistance plasmid did not disadvantage the mediating strain in the gut, even in the absence of antibiotic pressure. In contrast Lebek and Egger (1983), studying the same strains in vitro, found that in a chemostat the plasmid bearing strain was overgrown by the plasmid free strain. These results strongly suggest that in vitro interactions between E. coli strains cannot be directly extrapolated to in vivo conditions. For the determination of the no-effect level of antibiotic residue on the selection of R-factor in the gut, studies should be made in vivo.

Fig. 1

Competition between three isogenic strains of E. coli in gnotobiotic mice. Each point represents the mean log number of CFU/g faeces from three mice. Black triangles: nalidixic acid-tetracycline-R, Empty squares: rifampicin-R, Empty circles: streptomycin-R, i: inoculation.

Fig. 2

Effect of tetracycline on the interaction between two E. coli strains in gnotobiotic mice. 2A: tetracycline (16 μg/ml) was added into the drinking water at day 3. 2B: No tetracycline in the water. See Fig. 1 for symbols, except Solid black squares: rifampicin-tetracycline-R.

Fig. 3

Competition between two E. coli strains in gnotobiotic mice, in the presence of a human faecal flora. See. Fig. 2 for symbols +---+: total counts (anaerobic).