title: An IS257-derived hybrid promoter directs transcription of a tetA(K) tetracycline resistance gene in the Staphylococcus aureus chromosomal mec region.
abstract: Transcription of the tetA(K) tetracycline resistance determinant encoded by an IS257-flanked cointegrated copy of a pT181-like plasmid, located within the chromosomal mec region of a methicillin-resistant Staphylococcus aureus isolate, has been investigated. The results demonstrated that transcription of tetA(K) in this strain is directed by both an IS257-derived hybrid promoter, which is stronger than the native tetA(K) promoter in the autonomous form of pT181, and a complete outwardly directed promoter identified within one end of IS257. Despite lower gene dosage, the chromosomal configuration was shown to afford a higher level of resistance than that mediated by pT181 in an autonomous multicopy state. Furthermore, competition studies revealed that a strain carrying the chromosomal tetA(K) determinant exhibited a higher level of fitness in the presence of tetracycline but not in its absence. This finding suggests that tetracycline has been a selective factor in the emergence of strains carrying a cointegrated pT181-like plasmid in their chromosomes. The results highlight the potential of IS257 to influence the expression of neighboring genes, a property likely to enhance its capacity to mediate advantageous genetic rearrangements.
authors.affiliation: School of Biological Sciences, University of Sydney, New South Wales 2006, Australia.
authors.forename: A E
authors.initials: AE
authors.lastname: Simpson
authors.forename: R A
authors.initials: RA
authors.lastname: Skurray
authors.forename: N
authors.initials: N
authors.lastname: Firth
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002876:Chromosomes, Bacterial / Q000235:genetics; D004251:DNA Transposable Elements; D015964:Gene Expression Regulation, Bacterial; D016106:Methicillin Resistance / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D013752:Tetracycline / Q000494:pharmacology; D013753:Tetracycline Resistance; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D017920:Antiporters; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; C079051:tetA protein, Bacteria; D013752:Tetracycline