Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts

Jakob Frimodt-Møller, Elio Rossi, Janus Anders Juul Haagensen, Marilena Falcone, Søren Molin*, Helle Krogh Johansen

*Corresponding author for this work

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Abstract

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
Article number12512
JournalScientific Reports
Volume8
Number of pages13
ISSN2045-2322
DOIs
Publication statusPublished - 2018

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License

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