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Sökning: WFRF:(Praski Alzrigat Lisa) > Fitness cost constr...

Fitness cost constrains the spectrum of marR mutations in ciprofloxacin-resistant Escherichia coli : Multiple Antibiotic-Resistance, Gram-Negative Bacteria, Multidrug Efflux Pump, Urinary-Tract-Infections, Fluoroquinolone Resistance, Quinolone Resistance, Mechanisms, Expression, Sequence, Soxs

Praski Alzrigat, Lisa (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Diarmaid Hughes
Huseby, Douglas L (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Diarmaid Hughes
Brandis, Gerrit, 1985- (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Hughes, Diarmaid, 1956- (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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 (creator_code:org_t)
2017-08-17
2017
Engelska.
Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 2:11, s. 3016-3024
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Objectives: To determine whether the spectrum of mutations in marR in ciprofloxacin-resistant clinical isolates of Escherichia coli shows evidence of selection bias, either to reduce fitness costs, or to increase drug resistance. MarR is a repressor protein that regulates, via MarA, expression of the Mar regulon, including the multidrug efflux pump AcrAB-TolC. Methods: Isogenic strains carrying 36 different marR alleles identified in resistant clinical isolates, or selected for resistance in vitro, were constructed. Drug susceptibility and relative fitness in growth competition assays were measured for all strains. The expression level of marA, and of various efflux pump components, as a function of specific mutations in marR, was measured by qPCR. Results: The spectrum of genetic alterations in marR in clinical isolates is strongly biased against inactivating mutations. In general, the alleles found in clinical isolates conferred a lower level of resistance and imposed a lower growth fitness cost than mutations selected in vitro. The level of expression of MarA correlated well with the MIC of ciprofloxacin. This supports the functional connection between mutations in marR and reduced susceptibility to ciprofloxacin. Conclusions: Mutations in marR selected in ciprofloxacin-resistant clinical isolates are strongly biased against inactivating mutations. Selection favours mutant alleles that have the lowest fitness costs, even though these cause only modest reductions in drug susceptibility. This suggests that selection for high relative fitness is more important than selection for increased resistance in determining which alleles of marR will be selected in resistant clinical isolates.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Mikrobiologi
Microbiology

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