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Rigshospitalet - a part of Copenhagen University Hospital
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Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts

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  1. A prospective three-year follow-up study on the clinical significance of anti-neuronal antibodies in acute psychiatric disorders

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  2. Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients

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  3. A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk

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  4. Leukocyte telomere length is associated with elevated plasma glucose and HbA1c in young healthy men independent of birth weight

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  1. Primary ciliary dyskinesia patients have the same P. aeruginosa clone in sinuses and lungs

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  2. Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate

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  3. Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis

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In 474 genome sequenced Pseudomonas aeruginosa isolates from 34 cystic fibrosis (CF) patients, 40% of these harbor mutations in the mexZ gene encoding a negative regulator of the MexXY-OprM efflux pump associated with aminoglycoside and fluoroquinolone resistance. Surprisingly, resistance to aminoglycosides and fluoroquinolones of mexZ mutants was far below the breakpoint of clinical resistance. However, the fitness increase of the mutant bacteria in presence of the relevant antibiotics, as demonstrated in competition experiments between mutant and ancestor bacteria, showed that 1) very small phenotypic changes cause significant fitness increase with severe adaptive consequences, and 2) standardized phenotypic tests fail to detect such low-level variations. The frequent appearance of P. aeruginosa mexZ mutants in CF patients is directly connected to the intense use of the target antibiotics, and low-level antibiotic resistance, if left unnoticed, can result in accumulation of additional genetic changes leading to high-level resistance.

Original languageEnglish
JournalScientific Reports
Volume8
Issue number1
Pages (from-to)12512
ISSN2045-2322
DOIs
Publication statusPublished - 21 Aug 2018

ID: 56201373