title: Eﬄux in the Oral Metagenome: The Discovery of a Novel Tetracycline and Tigecycline ABC Transporter.
abstract: Antibiotic resistance in human bacterial pathogens and commensals is threatening our ability to treat infections and conduct common medical procedures. As novel antibiotics are discovered and marketed it is important that we understand how resistance to them may arise and know what environments may act as reservoirs for such resistance genes. In this study a tetracycline and tigecycline resistant clone was identified by screening a human saliva metagenomic library inEscherichia coliEPI300 on agar containing 5 μg/ml tetracycline. Sequencing of the DNA insert present within the tetracycline resistant clone revealed it to contain a 7,765 bp fragment harboring novel ABC half transporter genes,tetAB(60). Mutagenesis studies performed on these genes confirmed that they were responsible for the tetracycline and tigecycline resistance phenotypes. Growth studies performed usingE. coliEPI300 clones that harbored either the wild type, the mutated, or none of these genes indicated that there was a fitness cost associated with presence of these genes, with the isolate harboring both genes exhibiting a significantly slower growth than control strains. Given the emergence ofE. colistrains that are sensitive only to tigecycline and doxycycline it is concerning that such a resistance mechanism has been identified in the human oral cavity.
authors.affiliation: Department of Microbial Diseases, UCL Eastman Dental Institute, Faculty of Medical Sciences, University College LondonLondon, UK; Department of Bacteriology, Animal and Plant Health AgencyAddlestone, UK.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Reynolds
authors.affiliation: Department of Microbial Diseases, UCL Eastman Dental Institute, Faculty of Medical Sciences, University College London London, UK.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Roberts
authors.affiliation: Department of Microbial Diseases, UCL Eastman Dental Institute, Faculty of Medical Sciences, University College LondonLondon, UK; Department of Bacteriology, Animal and Plant Health AgencyAddlestone, UK.
authors.forename: Muna F
authors.initials: MF
authors.lastname: Anjum
keywords: ABC transporter; antibiotic resistance; fitness; metagenomics; tetracycline; tigecycline