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Development of antibiotic resistance and up-regulation of the antimutator gene pfpI in mutator Pseudomonas aeruginosa due to inactivation of two DNA oxidative repair genes (mutY, mutM). / Mandsberg, Lotte Frigaard; Macia, Maria D.; Bergmann, Kirsten R.; Christiansen, Lasse Engbo; Alhede, Morten; Kirkby, Nikolai; Hoiby, Niels; Oliver, Antonio; Ciofu, Oana.

In: F E M S Microbiology Letters, Vol. 324, No. 1, 2011, p. 28-37.

Publication: Research - peer-reviewJournal article – Annual report year: 2011

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Mandsberg, Lotte Frigaard; Macia, Maria D.; Bergmann, Kirsten R.; Christiansen, Lasse Engbo; Alhede, Morten; Kirkby, Nikolai; Hoiby, Niels; Oliver, Antonio; Ciofu, Oana / Development of antibiotic resistance and up-regulation of the antimutator gene pfpI in mutator Pseudomonas aeruginosa due to inactivation of two DNA oxidative repair genes (mutY, mutM).

In: F E M S Microbiology Letters, Vol. 324, No. 1, 2011, p. 28-37.

Publication: Research - peer-reviewJournal article – Annual report year: 2011

Bibtex

@article{767a8bdbaccc48eb94080c34f73f12bf,
title = "Development of antibiotic resistance and up-regulation of the antimutator gene pfpI in mutator Pseudomonas aeruginosa due to inactivation of two DNA oxidative repair genes (mutY, mutM)",
keywords = "Oxidative repair, Pseudomonas aeruginosa, Mutator",
publisher = "Wiley-Blackwell Publishing Ltd.",
author = "Mandsberg, {Lotte Frigaard} and Macia, {Maria D.} and Bergmann, {Kirsten R.} and Christiansen, {Lasse Engbo} and Morten Alhede and Nikolai Kirkby and Niels Hoiby and Antonio Oliver and Oana Ciofu",
year = "2011",
doi = "10.1111/j.1574-6968.2011.02383.x",
volume = "324",
number = "1",
pages = "28--37",
journal = "F E M S Microbiology Letters",
issn = "0378-1097",

}

RIS

TY - JOUR

T1 - Development of antibiotic resistance and up-regulation of the antimutator gene pfpI in mutator Pseudomonas aeruginosa due to inactivation of two DNA oxidative repair genes (mutY, mutM)

A1 - Mandsberg,Lotte Frigaard

A1 - Macia,Maria D.

A1 - Bergmann,Kirsten R.

A1 - Christiansen,Lasse Engbo

A1 - Alhede,Morten

A1 - Kirkby,Nikolai

A1 - Hoiby,Niels

A1 - Oliver,Antonio

A1 - Ciofu,Oana

AU - Mandsberg,Lotte Frigaard

AU - Macia,Maria D.

AU - Bergmann,Kirsten R.

AU - Christiansen,Lasse Engbo

AU - Alhede,Morten

AU - Kirkby,Nikolai

AU - Hoiby,Niels

AU - Oliver,Antonio

AU - Ciofu,Oana

PB - Wiley-Blackwell Publishing Ltd.

PY - 2011

Y1 - 2011

N2 - Prevention and correction of oxidative DNA lesions in Pseudomonas aeruginosa is ensured by the DNA oxidative repair system (GO). Single inactivation of mutT, mutY and mutM involved in GO led to elevated mutation rates (MRs) that correlated to increased development of resistance to antibiotics. In this study, we constructed a double mutant in mutY and mutM (PAOMY-Mgm) and characterized the phenotype and the gene expression profile using microarray and RT-PCR. PAOMY-Mgm presented 28-fold increases in MR compared with wild-type reference strain PAO1. In comparison, the PAOMYgm (mutY) single mutant showed only a fivefold increase, whereas the single mutant PAOMMgm (mutM) showed a nonsignificant increase in MR compared with PAO1 and the single mutants. Mutations in the regulator nfxB leading to hyperexpression of MexCD-OprJ efflux pump were found as the mechanism of resistance to ciprofloxacin in the double mutant. A better fitness of the mutator compared with PAO1 was found in growth competition experiments in the presence of ciprofloxacin at concentrations just below minimal inhibitory concentration. Up-regulation of the antimutator gene pfpI, that has been shown to provide protection to oxidative stress, was found in PAOMYMgm compared with PAO1. In conclusion, we showed that MutY and MutM are cooperating in the GO of P. aeruginosa, and that oxidative DNA lesions might represent an oxidative stress for the bacteria.

AB - Prevention and correction of oxidative DNA lesions in Pseudomonas aeruginosa is ensured by the DNA oxidative repair system (GO). Single inactivation of mutT, mutY and mutM involved in GO led to elevated mutation rates (MRs) that correlated to increased development of resistance to antibiotics. In this study, we constructed a double mutant in mutY and mutM (PAOMY-Mgm) and characterized the phenotype and the gene expression profile using microarray and RT-PCR. PAOMY-Mgm presented 28-fold increases in MR compared with wild-type reference strain PAO1. In comparison, the PAOMYgm (mutY) single mutant showed only a fivefold increase, whereas the single mutant PAOMMgm (mutM) showed a nonsignificant increase in MR compared with PAO1 and the single mutants. Mutations in the regulator nfxB leading to hyperexpression of MexCD-OprJ efflux pump were found as the mechanism of resistance to ciprofloxacin in the double mutant. A better fitness of the mutator compared with PAO1 was found in growth competition experiments in the presence of ciprofloxacin at concentrations just below minimal inhibitory concentration. Up-regulation of the antimutator gene pfpI, that has been shown to provide protection to oxidative stress, was found in PAOMYMgm compared with PAO1. In conclusion, we showed that MutY and MutM are cooperating in the GO of P. aeruginosa, and that oxidative DNA lesions might represent an oxidative stress for the bacteria.

KW - Oxidative repair

KW - Pseudomonas aeruginosa

KW - Mutator

U2 - 10.1111/j.1574-6968.2011.02383.x

DO - 10.1111/j.1574-6968.2011.02383.x

JO - F E M S Microbiology Letters

JF - F E M S Microbiology Letters

SN - 0378-1097

IS - 1

VL - 324

SP - 28

EP - 37

ER -