The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions

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The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions. / Jochumsen, Nicholas; Marvig, Rasmus L.; Damkiaer, Soren; Jensen, Rune Lyngklip; Paulander, Wilhelm; Molin, Soren; Jelsbak, Lars; Folkesson, Anders.

I: Nature Communications, Bind 7, 13002, 03.10.2016.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Jochumsen, N, Marvig, RL, Damkiaer, S, Jensen, RL, Paulander, W, Molin, S, Jelsbak, L & Folkesson, A 2016, 'The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions', Nature Communications, bind 7, 13002. https://doi.org/10.1038/ncomms13002

APA

Jochumsen, N., Marvig, R. L., Damkiaer, S., Jensen, R. L., Paulander, W., Molin, S., Jelsbak, L., & Folkesson, A. (2016). The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions. Nature Communications, 7, [13002]. https://doi.org/10.1038/ncomms13002

Vancouver

Jochumsen N, Marvig RL, Damkiaer S, Jensen RL, Paulander W, Molin S o.a. The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions. Nature Communications. 2016 okt. 3;7. 13002. https://doi.org/10.1038/ncomms13002

Author

Jochumsen, Nicholas ; Marvig, Rasmus L. ; Damkiaer, Soren ; Jensen, Rune Lyngklip ; Paulander, Wilhelm ; Molin, Soren ; Jelsbak, Lars ; Folkesson, Anders. / The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions. I: Nature Communications. 2016 ; Bind 7.

Bibtex

@article{4296f8168551420baf7c376a062e3d55,
title = "The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions",
abstract = "Colistin is an antimicrobial peptide that has become the only remaining alternative for the treatment of multidrug-resistant Gram-negative bacterial infections, but little is known of how clinical levels of colistin resistance evolve. We use in vitro experimental evolution and whole-genome sequencing of colistin-resistant Pseudomonas aeruginosa isolates from cystic fibrosis patients to reconstruct the molecular evolutionary pathways open for high-level colistin resistance. We show that the evolution of resistance is a complex, multistep process that requires mutation in at least five independent loci that synergistically create the phenotype. Strong intergenic epistasis limits the number of possible evolutionary pathways to resistance. Mutations in transcriptional regulators are essential for resistance evolution and function as nodes that potentiate further evolution towards higher resistance by functionalizing and increasing the effect of the other mutations. These results add to our understanding of clinical antimicrobial peptide resistance and the prediction of resistance evolution.",
author = "Nicholas Jochumsen and Marvig, {Rasmus L.} and Soren Damkiaer and Jensen, {Rune Lyngklip} and Wilhelm Paulander and Soren Molin and Lars Jelsbak and Anders Folkesson",
year = "2016",
month = oct,
day = "3",
doi = "10.1038/ncomms13002",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions

AU - Jochumsen, Nicholas

AU - Marvig, Rasmus L.

AU - Damkiaer, Soren

AU - Jensen, Rune Lyngklip

AU - Paulander, Wilhelm

AU - Molin, Soren

AU - Jelsbak, Lars

AU - Folkesson, Anders

PY - 2016/10/3

Y1 - 2016/10/3

N2 - Colistin is an antimicrobial peptide that has become the only remaining alternative for the treatment of multidrug-resistant Gram-negative bacterial infections, but little is known of how clinical levels of colistin resistance evolve. We use in vitro experimental evolution and whole-genome sequencing of colistin-resistant Pseudomonas aeruginosa isolates from cystic fibrosis patients to reconstruct the molecular evolutionary pathways open for high-level colistin resistance. We show that the evolution of resistance is a complex, multistep process that requires mutation in at least five independent loci that synergistically create the phenotype. Strong intergenic epistasis limits the number of possible evolutionary pathways to resistance. Mutations in transcriptional regulators are essential for resistance evolution and function as nodes that potentiate further evolution towards higher resistance by functionalizing and increasing the effect of the other mutations. These results add to our understanding of clinical antimicrobial peptide resistance and the prediction of resistance evolution.

AB - Colistin is an antimicrobial peptide that has become the only remaining alternative for the treatment of multidrug-resistant Gram-negative bacterial infections, but little is known of how clinical levels of colistin resistance evolve. We use in vitro experimental evolution and whole-genome sequencing of colistin-resistant Pseudomonas aeruginosa isolates from cystic fibrosis patients to reconstruct the molecular evolutionary pathways open for high-level colistin resistance. We show that the evolution of resistance is a complex, multistep process that requires mutation in at least five independent loci that synergistically create the phenotype. Strong intergenic epistasis limits the number of possible evolutionary pathways to resistance. Mutations in transcriptional regulators are essential for resistance evolution and function as nodes that potentiate further evolution towards higher resistance by functionalizing and increasing the effect of the other mutations. These results add to our understanding of clinical antimicrobial peptide resistance and the prediction of resistance evolution.

U2 - 10.1038/ncomms13002

DO - 10.1038/ncomms13002

M3 - Journal article

C2 - 27694971

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 13002

ER -

ID: 169107883