title: Restored fitness leads to long-term persistence of resistant Bacteroides strains in the human intestine.
abstract: Acquired antibiotic resistance typically confers a cost to the bacteria, but these costs can be reduced by genetic compensation over time. The fitness of two Bacteroides thetaiotaomicron clones consecutively isolated in vivo was studied using an in vitro pair-wise competition method. The isolates derived from faecal samples of two clindamycin-exposed healthy volunteers and the two B. thetaiotaomicron clone types could be followed up to 18 months in these two subjects. The two clones were originally susceptible to clindamycin and lacked erm genes; however, after 7 days of clindamycin administration they carried the erm (erythromycin methylase)(G) or (F) gene, respectively, and expressed phenotypic clindamycin resistance. The initial cost of acquired resistance was high as seen in the in vitro pair-wise competition experiments. At 2 weeks post-administration, no growth disadvantage was detected for isolates of either of the two clones in the in vitro experiments and this regained fitness remained for isolates collected up to 18 months. Competition analysis of an in vitro isolated erm(G) positive transconjugant also demonstrated an initial reduction of fitness that was restored over time. The results indicate that the biological cost associated with a resistance gene can rapidly be compensated during in vivo growth. Thus, once the resistant clone has gained its resistance determinant it will be difficult to eliminate.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology, F82, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden. sonja.lofmark@ki.se
authors.forename: Sonja
authors.initials: S
authors.lastname: Löfmark
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jernberg
authors.forename: Hanna
authors.initials: H
authors.lastname: Billström
authors.forename: Dan I
authors.initials: DI
authors.lastname: Andersson
authors.forename: Charlotta
authors.initials: C
authors.lastname: Edlund
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D001439:Bacteroides / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D002981:Clindamycin / Q000008:administration & dosage / Q000494:pharmacology*; D003227:Conjugation, Genetic; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008780:Methyltransferases / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002981:Clindamycin; D008780:Methyltransferases; C437393:ErmF protein, Bacteroides