Plasmid-mediated susceptibility to intestinal microbial antagonisms in Escherichia coli.

Self-transferable plasmid pIP1100 confers to Escherichia coli an unusually high level of resistance (1 to 2 mg/ml) to erythromycin by production of an erythromycin esterase. The effect of pIP1100 on the destiny of E. coli strains in the intestines of gnotobiotic mice was studied. In germfree mice, pIP1100 was efficiently transferred to a plasmid-free E. coli recipient. Intestinal counts of the donor, the recipient, and the transconjugants were greater than 8.5 log CFU/g of feces. When erythromycin was added to the diet of the mice, counts of the plasmid-bearing strains were only slightly lowered and partial inactivation of erythromycin was observed in the feces. Transfer of pIP1100 also occurred in human-flora-associated mice. In this model all the E. coli strains were subject to microbial antagonisms caused by the anaerobic components of the flora. However, strains harboring pIP1100 were strongly inhibited (less than 2.5 log CFU/g of feces), whereas their plasmid-free counterparts persisted at much higher population levels (greater than 5.2 log CFU/g of feces). The ecological disadvantage conferred by pIP1100 to E. coli when a complex human flora was concomitantly present in the intestine of the mice persisted during erythromycin administration. These results provide an explanation for the low incidence of isolation of highly erythromycin-resistant E. coli strains despite the extensive use of the antibiotic.