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The Capital Region of Denmark - 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. Detection of biological signals from a live mammalian muscle using an early stage diamond quantum sensor

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  2. Infants with congenital heart defects have reduced brain volumes

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  3. Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study

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  4. Extrarenal expression of α-klotho, the kidney related longevity gene, in Heterocephalus glaber, the long living Naked Mole Rat

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  1. Update 2016-2018 of the Nationwide Danish Fungaemia Surveillance Study: Epidemiologic Changes in a 15-Year Perspective

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  2. Omics-based tracking of Pseudomonas aeruginosa persistence in "eradicated" cystic fibrosis patients.

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  3. Bacterial persisters in long-term infection: Emergence and fitness in a complex host environment

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  4. Gene Loss and Acquisition in Lineages of Pseudomonas aeruginosa Evolving in Cystic Fibrosis Patient Airways

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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