Lack of glyoxylate shunt dysregulates iron homeostasis in pseudomonas aeruginosa

Sunhee Ha, Bora Shin, Woojun Park

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The aceA and glcB genes, encoding isocitrate lyase (ICL) and malate synthase, respectively, are not in an operon in many bacteria, including Pseudomonas aeruginosa, unlike in Escherichia coli. Here, we show that expression of aceA in P. aeruginosa is specifically upregulated under H2O2-induced oxidative stress and under iron-limiting conditions. In contrast, the addition of exogenous redox active compounds or antibiotics increases the expression of glcB. The transcriptional start sites of aceA under iron-limiting conditions and in the presence of iron were found to be identical by 5′ RACE. Interestingly, the enzymatic activities of ICL and isocitrate dehydrogenase had opposite responses under different iron conditions, suggesting that the glyoxylate shunt (GS) might be important under iron-limiting conditions. Remarkably, the intracellular iron concentration was lower while the iron demand was higher in the GS-activated cells growing on acetate compared to cells growing on glucose. Absence of GS dysregulated iron homeostasis led to changes in the cellular iron pool, with higher intracellular chelatable iron levels. In addition, GS mutants were found to have higher cytochrome c oxidase activity on iron-supplemented agar plates of minimal media, which promoted the growth of the GS mutants. However, deletion of the GS genes resulted in higher sensitivity to a high concentration of H2O2, presumably due to iron-mediated killing. In conclusion, the GS system appears to be tightly linked to iron homeostasis in the promotion of P. aeruginosa survival under oxidative stress.

Original languageEnglish
Article number000623
Pages (from-to)587-599
Number of pages13
JournalMicrobiology (United Kingdom)
Volume164
Issue number4
DOIs
Publication statusPublished - 2018 Apr 1

Fingerprint

Pseudomonas aeruginosa
Homeostasis
Iron
Isocitrate Lyase
glyoxylic acid
Oxidative Stress
Malate Synthase
Isocitrate Dehydrogenase
Electron Transport Complex IV
Operon
Genes
Agar
Oxidation-Reduction
Acetates
Escherichia coli
Anti-Bacterial Agents
Bacteria
Glucose

Keywords

  • Bacteria
  • Gene expression
  • Glyoxylate bypass
  • Iron
  • Oxidative stress
  • TCA cycle

ASJC Scopus subject areas

  • Microbiology

Cite this

Lack of glyoxylate shunt dysregulates iron homeostasis in pseudomonas aeruginosa. / Ha, Sunhee; Shin, Bora; Park, Woojun.

In: Microbiology (United Kingdom), Vol. 164, No. 4, 000623, 01.04.2018, p. 587-599.

Research output: Contribution to journalArticle

@article{9d711f26a6214b2f9d7647774bb0eea3,
title = "Lack of glyoxylate shunt dysregulates iron homeostasis in pseudomonas aeruginosa",
abstract = "The aceA and glcB genes, encoding isocitrate lyase (ICL) and malate synthase, respectively, are not in an operon in many bacteria, including Pseudomonas aeruginosa, unlike in Escherichia coli. Here, we show that expression of aceA in P. aeruginosa is specifically upregulated under H2O2-induced oxidative stress and under iron-limiting conditions. In contrast, the addition of exogenous redox active compounds or antibiotics increases the expression of glcB. The transcriptional start sites of aceA under iron-limiting conditions and in the presence of iron were found to be identical by 5′ RACE. Interestingly, the enzymatic activities of ICL and isocitrate dehydrogenase had opposite responses under different iron conditions, suggesting that the glyoxylate shunt (GS) might be important under iron-limiting conditions. Remarkably, the intracellular iron concentration was lower while the iron demand was higher in the GS-activated cells growing on acetate compared to cells growing on glucose. Absence of GS dysregulated iron homeostasis led to changes in the cellular iron pool, with higher intracellular chelatable iron levels. In addition, GS mutants were found to have higher cytochrome c oxidase activity on iron-supplemented agar plates of minimal media, which promoted the growth of the GS mutants. However, deletion of the GS genes resulted in higher sensitivity to a high concentration of H2O2, presumably due to iron-mediated killing. In conclusion, the GS system appears to be tightly linked to iron homeostasis in the promotion of P. aeruginosa survival under oxidative stress.",
keywords = "Bacteria, Gene expression, Glyoxylate bypass, Iron, Oxidative stress, TCA cycle",
author = "Sunhee Ha and Bora Shin and Woojun Park",
year = "2018",
month = "4",
day = "1",
doi = "10.1099/mic.0.000623",
language = "English",
volume = "164",
pages = "587--599",
journal = "Microbiology (United Kingdom)",
issn = "1350-0872",
publisher = "Society for General Microbiology",
number = "4",

}

TY - JOUR

T1 - Lack of glyoxylate shunt dysregulates iron homeostasis in pseudomonas aeruginosa

AU - Ha, Sunhee

AU - Shin, Bora

AU - Park, Woojun

PY - 2018/4/1

Y1 - 2018/4/1

N2 - The aceA and glcB genes, encoding isocitrate lyase (ICL) and malate synthase, respectively, are not in an operon in many bacteria, including Pseudomonas aeruginosa, unlike in Escherichia coli. Here, we show that expression of aceA in P. aeruginosa is specifically upregulated under H2O2-induced oxidative stress and under iron-limiting conditions. In contrast, the addition of exogenous redox active compounds or antibiotics increases the expression of glcB. The transcriptional start sites of aceA under iron-limiting conditions and in the presence of iron were found to be identical by 5′ RACE. Interestingly, the enzymatic activities of ICL and isocitrate dehydrogenase had opposite responses under different iron conditions, suggesting that the glyoxylate shunt (GS) might be important under iron-limiting conditions. Remarkably, the intracellular iron concentration was lower while the iron demand was higher in the GS-activated cells growing on acetate compared to cells growing on glucose. Absence of GS dysregulated iron homeostasis led to changes in the cellular iron pool, with higher intracellular chelatable iron levels. In addition, GS mutants were found to have higher cytochrome c oxidase activity on iron-supplemented agar plates of minimal media, which promoted the growth of the GS mutants. However, deletion of the GS genes resulted in higher sensitivity to a high concentration of H2O2, presumably due to iron-mediated killing. In conclusion, the GS system appears to be tightly linked to iron homeostasis in the promotion of P. aeruginosa survival under oxidative stress.

AB - The aceA and glcB genes, encoding isocitrate lyase (ICL) and malate synthase, respectively, are not in an operon in many bacteria, including Pseudomonas aeruginosa, unlike in Escherichia coli. Here, we show that expression of aceA in P. aeruginosa is specifically upregulated under H2O2-induced oxidative stress and under iron-limiting conditions. In contrast, the addition of exogenous redox active compounds or antibiotics increases the expression of glcB. The transcriptional start sites of aceA under iron-limiting conditions and in the presence of iron were found to be identical by 5′ RACE. Interestingly, the enzymatic activities of ICL and isocitrate dehydrogenase had opposite responses under different iron conditions, suggesting that the glyoxylate shunt (GS) might be important under iron-limiting conditions. Remarkably, the intracellular iron concentration was lower while the iron demand was higher in the GS-activated cells growing on acetate compared to cells growing on glucose. Absence of GS dysregulated iron homeostasis led to changes in the cellular iron pool, with higher intracellular chelatable iron levels. In addition, GS mutants were found to have higher cytochrome c oxidase activity on iron-supplemented agar plates of minimal media, which promoted the growth of the GS mutants. However, deletion of the GS genes resulted in higher sensitivity to a high concentration of H2O2, presumably due to iron-mediated killing. In conclusion, the GS system appears to be tightly linked to iron homeostasis in the promotion of P. aeruginosa survival under oxidative stress.

KW - Bacteria

KW - Gene expression

KW - Glyoxylate bypass

KW - Iron

KW - Oxidative stress

KW - TCA cycle

UR - http://www.scopus.com/inward/record.url?scp=85045152131&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045152131&partnerID=8YFLogxK

U2 - 10.1099/mic.0.000623

DO - 10.1099/mic.0.000623

M3 - Article

C2 - 29465342

AN - SCOPUS:85045152131

VL - 164

SP - 587

EP - 599

JO - Microbiology (United Kingdom)

JF - Microbiology (United Kingdom)

SN - 1350-0872

IS - 4

M1 - 000623

ER -