title: Evidence of increased spread and establishment of plasmid RP4 in the intestine under sub-inhibitory tetracycline concentrations.
abstract: The consequences of using anti-microbial agents in a complex ecosystem like the animal intestine can be difficult to predict. We have looked at effects of modulations in growth of competing intestinal bacteria on transfer and establishment of new genetic elements in the intestinal microflora. For this purpose, we used tetracycline, which gradually reduces the growth rate of tetracycline-sensitive bacteria, as the concentration of this drug is increased. The effect of tetracycline on transfer and establishment of the plasmid RP4, which encodes resistance to this drug, in populations of Escherichia coli BJ4 colonizing the intestine was investigated. A tetracycline-sensitive E. coli BJ4 strain was allowed to establish in the gastrointestinal tract of mice, where after an isogenic E. coli BJ4 carrying RP4 was given to the mice per os. Tetracycline in the drinking water given to the animals was kept in concentrations that allowed the sensitive recipient strain to colonize the gut. A given 'window' between the highest and the lowest antibiotic doses tested was shown to be optimal for the establishment of transconjugants in the intestine. These observations are important for the evaluation of the effect of a given drug on the intestinal ecosystem. A reduced potential for growth of a given bacterial species, caused by the presence of sub-inhibitory concentrations of a bacteriostatic antibiotic, will facilitate establishment of competing (i.e. closely related) organisms, which have acquired resistance genes and therefore grow well in the presence of the drug.
authors.affiliation: Department of Gastrointestinal Infections, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: Tine Rask
authors.initials: TR
authors.lastname: Licht
authors.forename: Carsten
authors.initials: C
authors.lastname: Struve
authors.forename: Bjarke Bak
authors.initials: BB
authors.lastname: Christensen
authors.forename: Rikke Lykke
authors.initials: RL
authors.lastname: Poulsen
authors.forename: Søren
authors.initials: S
authors.lastname: Molin
authors.forename: Karen A
authors.initials: KA
authors.lastname: Krogfelt