Intergenic evolution during host adaptation increases expression of the metallophore pseudopaline in Pseudomonas aeruginosa

Grith Miriam Maigaard Hermansen, Morten Lindqvist Hansen, Seyed Mohammad Hossein Khademi, Lars Jelsbak*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Regulating intracellular levels of biological metal ions is essential for all bacterial species, as they are needed for virulence and a range of metabolic processes. Zinc is the second most abundant metal ion in Pseudomonas aeruginosa, but little is known about its regulation. Recent studies have identified a novel operon, zrmABCD (also called cntOLMI), encoding a metallophore system (pseudopaline) involved in zinc acquisition. Expression of this operon has been implicated in human infections and is regulated by the transcriptional regulator Zur (Zn2+ uptake regulator). In this study, we show that the intergenic promoter region in front of zrmABCD is a target for recurrent adaptive mutations during chronic infection of cystic fibrosis (CF) patients. We characterize the inter- and intraclonal sequence polymorphisms found in the promoter region of the metallophore system and find that most alterations increase promoter activity. One of the evolved promoters displays a more than 10-fold increase compared to the ancestral strain due to the combined effect of an altered binding site of Zur and changes to the RpoD-binding motif. This specific evolved promoter responds differently to changes in metal ion concentrations in chelated medium. We have previously shown that P. aeruginosa evolves toward iron acquisition from haemoglobin during long-term CF infections. We hereby provide the second example of adaptive mutations targeting intergenic regions that affect metal ion uptake systems during CF infections, and the first involving zinc uptake. Our results suggest that the scarcity of metal ions (including iron and zinc) is an important evolutionary driver in CF host adaptation.

Original languageEnglish
JournalMicrobiology
Volume164
Issue number8
Pages (from-to)1038-1047
ISSN1350-0872
DOIs
Publication statusPublished - 2018

Keywords

  • Metallophore
  • Biological metal ions
  • Adaptation
  • Zinc
  • Pseudomonas aeruginosa
  • Cystic fibrosis

Cite this

Hermansen, Grith Miriam Maigaard ; Hansen, Morten Lindqvist ; Khademi, Seyed Mohammad Hossein ; Jelsbak, Lars. / Intergenic evolution during host adaptation increases expression of the metallophore pseudopaline in Pseudomonas aeruginosa. In: Microbiology. 2018 ; Vol. 164, No. 8. pp. 1038-1047.
@article{9928f15683534285b96ff956d38ea459,
title = "Intergenic evolution during host adaptation increases expression of the metallophore pseudopaline in Pseudomonas aeruginosa",
abstract = "Regulating intracellular levels of biological metal ions is essential for all bacterial species, as they are needed for virulence and a range of metabolic processes. Zinc is the second most abundant metal ion in Pseudomonas aeruginosa, but little is known about its regulation. Recent studies have identified a novel operon, zrmABCD (also called cntOLMI), encoding a metallophore system (pseudopaline) involved in zinc acquisition. Expression of this operon has been implicated in human infections and is regulated by the transcriptional regulator Zur (Zn2+ uptake regulator). In this study, we show that the intergenic promoter region in front of zrmABCD is a target for recurrent adaptive mutations during chronic infection of cystic fibrosis (CF) patients. We characterize the inter- and intraclonal sequence polymorphisms found in the promoter region of the metallophore system and find that most alterations increase promoter activity. One of the evolved promoters displays a more than 10-fold increase compared to the ancestral strain due to the combined effect of an altered binding site of Zur and changes to the RpoD-binding motif. This specific evolved promoter responds differently to changes in metal ion concentrations in chelated medium. We have previously shown that P. aeruginosa evolves toward iron acquisition from haemoglobin during long-term CF infections. We hereby provide the second example of adaptive mutations targeting intergenic regions that affect metal ion uptake systems during CF infections, and the first involving zinc uptake. Our results suggest that the scarcity of metal ions (including iron and zinc) is an important evolutionary driver in CF host adaptation.",
keywords = "Metallophore, Biological metal ions, Adaptation, Zinc, Pseudomonas aeruginosa, Cystic fibrosis",
author = "Hermansen, {Grith Miriam Maigaard} and Hansen, {Morten Lindqvist} and Khademi, {Seyed Mohammad Hossein} and Lars Jelsbak",
year = "2018",
doi = "10.1099/mic.0.000687",
language = "English",
volume = "164",
pages = "1038--1047",
journal = "Microbiology",
issn = "1350-0872",
publisher = "Society for General Microbiology",
number = "8",

}

Intergenic evolution during host adaptation increases expression of the metallophore pseudopaline in Pseudomonas aeruginosa. / Hermansen, Grith Miriam Maigaard; Hansen, Morten Lindqvist; Khademi, Seyed Mohammad Hossein; Jelsbak, Lars.

In: Microbiology, Vol. 164, No. 8, 2018, p. 1038-1047.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Intergenic evolution during host adaptation increases expression of the metallophore pseudopaline in Pseudomonas aeruginosa

AU - Hermansen, Grith Miriam Maigaard

AU - Hansen, Morten Lindqvist

AU - Khademi, Seyed Mohammad Hossein

AU - Jelsbak, Lars

PY - 2018

Y1 - 2018

N2 - Regulating intracellular levels of biological metal ions is essential for all bacterial species, as they are needed for virulence and a range of metabolic processes. Zinc is the second most abundant metal ion in Pseudomonas aeruginosa, but little is known about its regulation. Recent studies have identified a novel operon, zrmABCD (also called cntOLMI), encoding a metallophore system (pseudopaline) involved in zinc acquisition. Expression of this operon has been implicated in human infections and is regulated by the transcriptional regulator Zur (Zn2+ uptake regulator). In this study, we show that the intergenic promoter region in front of zrmABCD is a target for recurrent adaptive mutations during chronic infection of cystic fibrosis (CF) patients. We characterize the inter- and intraclonal sequence polymorphisms found in the promoter region of the metallophore system and find that most alterations increase promoter activity. One of the evolved promoters displays a more than 10-fold increase compared to the ancestral strain due to the combined effect of an altered binding site of Zur and changes to the RpoD-binding motif. This specific evolved promoter responds differently to changes in metal ion concentrations in chelated medium. We have previously shown that P. aeruginosa evolves toward iron acquisition from haemoglobin during long-term CF infections. We hereby provide the second example of adaptive mutations targeting intergenic regions that affect metal ion uptake systems during CF infections, and the first involving zinc uptake. Our results suggest that the scarcity of metal ions (including iron and zinc) is an important evolutionary driver in CF host adaptation.

AB - Regulating intracellular levels of biological metal ions is essential for all bacterial species, as they are needed for virulence and a range of metabolic processes. Zinc is the second most abundant metal ion in Pseudomonas aeruginosa, but little is known about its regulation. Recent studies have identified a novel operon, zrmABCD (also called cntOLMI), encoding a metallophore system (pseudopaline) involved in zinc acquisition. Expression of this operon has been implicated in human infections and is regulated by the transcriptional regulator Zur (Zn2+ uptake regulator). In this study, we show that the intergenic promoter region in front of zrmABCD is a target for recurrent adaptive mutations during chronic infection of cystic fibrosis (CF) patients. We characterize the inter- and intraclonal sequence polymorphisms found in the promoter region of the metallophore system and find that most alterations increase promoter activity. One of the evolved promoters displays a more than 10-fold increase compared to the ancestral strain due to the combined effect of an altered binding site of Zur and changes to the RpoD-binding motif. This specific evolved promoter responds differently to changes in metal ion concentrations in chelated medium. We have previously shown that P. aeruginosa evolves toward iron acquisition from haemoglobin during long-term CF infections. We hereby provide the second example of adaptive mutations targeting intergenic regions that affect metal ion uptake systems during CF infections, and the first involving zinc uptake. Our results suggest that the scarcity of metal ions (including iron and zinc) is an important evolutionary driver in CF host adaptation.

KW - Metallophore

KW - Biological metal ions

KW - Adaptation

KW - Zinc

KW - Pseudomonas aeruginosa

KW - Cystic fibrosis

U2 - 10.1099/mic.0.000687

DO - 10.1099/mic.0.000687

M3 - Journal article

C2 - 29969091

VL - 164

SP - 1038

EP - 1047

JO - Microbiology

JF - Microbiology

SN - 1350-0872

IS - 8

ER -