title: Antibiotic resistance correlates with transmission in plasmid evolution.
abstract: Conjugative (horizontally transmissible) plasmids are autonomous replicators, whose "self-interests" do not necessarily overlap with those of their hosts. This situation causes plasmids and bacteria to sometimes experience differing selection pressures. Escherichia coli plasmid pB15 contains genes for resistance to several antibiotics, including tetracycline. When plasmid-bearing cells were experimentally evolved in the laboratory, changes in resistance level in the unselected tetracycline marker coincided with changes in plasmid rates of vertical versus horizontal transmission. Here, we used minimum inhibitory assays that measure resistance levels as quantitative traits to determine phenotypic correlations among plasmid characters and to estimate divergence among plasmid lineages. Results suggested that plasmid-level evolution led to formation of two phenotypically dissimilar groups: virulent (highly infectious) and avirulent (weakly infectious) plasmids. In contrast, measures of carbon-source utilization, and fitness assays relative to a common competitor revealed that bacterial hosts generally converged in phenotypic performance, despite divergence among their associated plasmids. Preliminary sequence analyses suggested that divergence in plasmid conjugation was due to altered configurations of a shufflon region (a site-specific recombination system), where genetic rearrangements affect conjugative ability. Furthermore, we proposed that correlated resistance and transmission in pB15 derivatives were caused by a tetracycline-resistance transposon inserted into a transfer operon, allowing transcription from its promoter to simultaneously affect both plasmid resistance and transmission.
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06520. paul.turner@yale.edu.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Turner
authors.forename: Elizabeth S C P
authors.initials: ES
authors.lastname: Williams
authors.forename: Chijioke
authors.initials: C
authors.lastname: Okeke
authors.forename: Vaughn S
authors.initials: VS
authors.lastname: Cooper
authors.forename: Siobain
authors.initials: S
authors.lastname: Duffy
authors.forename: John E
authors.initials: JE
authors.lastname: Wertz
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003227:Conjugation, Genetic; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D010957:Plasmids / Q000235:genetics*; D013752:Tetracycline / Q000494:pharmacology; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D013752:Tetracycline
keywords: Bacteria; Escherichia coli; experimental evolution; shufflon; virulence