RESUMO
AxyXY-OprZ is an RND-type efflux system that confers innate aminoglycoside resistance to Achromobacter spp. We investigated here a putative TetR family transcriptional regulator encoded by the axyZ gene located upstream of axyXY-oprZ An in-frame axyZ gene deletion assay led to increased MICs of antibiotic substrates of the efflux system, including aminoglycosides, cefepime, fluoroquinolones, tetracyclines, and erythromycin, indicating that the product of axyZ negatively regulates expression of axyXY-oprZ Moreover, we identified an amino acid substitution at position 29 of AxyZ (V29G) in a clinical Achromobacter strain that occurred during the course of chronic respiratory tract colonization in a cystic fibrosis (CF) patient. This substitution, also detected in three other strains exposed in vitro to tobramycin, led to an increase in the axyY transcription level (5- to 17-fold) together with an increase in antibiotic resistance level. This overproduction of AxyXY-OprZ is the first description of antibiotic resistance acquisition due to modification of a chromosomally encoded mechanism in Achromobacter and might have an impact on the management of infected CF patients. Indeed, tobramycin is widely used for aerosol therapy within this population, and we have demonstrated that it easily selects mutants with increased MICs of not only aminoglycosides but also fluoroquinolones, cefepime, and tetracyclines.
Assuntos
Achromobacter/genética , Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Membrana Transportadoras/genética , Tobramicina/farmacologia , Transativadores/genética , Achromobacter/efeitos dos fármacos , Achromobacter/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Transativadores/biossínteseRESUMO
The Streptomyces sanglieri bacteriophages AxeJC, Cumberbatch, Eastland, Eklok, HFrancette, Ignacio, Piccadilly, and Vondra form a novel actinobacteriophage cluster, BP. These siphoviruses have circularly permuted genomes with an average size of 37,700 bp and a GC content of 71%. Each genome contains approximately 58 protein-coding genes, with no tRNAs.