Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex I

Abstract Pseudomonas aeruginosa is a Gram‐negative bacterium of the proteobacteria class, and one of the most common causes of nosocomial infections. For example, it causes chronic pneumonia in cystic fibrosis patients. Patient sputum contains 2‐heptyl‐4‐hydroxyquinoline N‐oxide [HQNO] and Pseudomon...

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Main Authors: Bettina Rieger, Sven Thierbach, Miriam Ommer, Finja S.V. Dienhart, Susanne Fetzner, Karin B. Busch
Format: Article
Language:English
Published: Wiley 2020-03-01
Series:FASEB BioAdvances
Subjects:
Online Access:https://doi.org/10.1096/fba.2019-00084
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author Bettina Rieger
Sven Thierbach
Miriam Ommer
Finja S.V. Dienhart
Susanne Fetzner
Karin B. Busch
author_facet Bettina Rieger
Sven Thierbach
Miriam Ommer
Finja S.V. Dienhart
Susanne Fetzner
Karin B. Busch
author_sort Bettina Rieger
collection DOAJ
description Abstract Pseudomonas aeruginosa is a Gram‐negative bacterium of the proteobacteria class, and one of the most common causes of nosocomial infections. For example, it causes chronic pneumonia in cystic fibrosis patients. Patient sputum contains 2‐heptyl‐4‐hydroxyquinoline N‐oxide [HQNO] and Pseudomonas quorum sensing molecules such as the Pseudomonas quinolone signal [PQS]. It is known that HQNO inhibits the enzyme activity of mitochondrial and bacterial complex III at the Qi (quinone reduction) site, but the target of PQS is not known. In this work we have shown that PQS has a negative effect on mitochondrial respiration in HeLa and A549 cells. It specifically inhibits the complex I of the respiratory chain. In vitro analyses showed a partially competitive inhibition with respect to ubiquinone at the IQ site. In competing studies with Rotenone, PQS suppressed the ROS‐promoting effect of Rotenone, which is typical for a B‐type inhibitor. Prolonged incubation with PQS also had an effect on the activity of complex III.
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spelling doaj.art-7d2b62f3991144eb853ec21d1f0a92002022-12-21T22:40:14ZengWileyFASEB BioAdvances2573-98322020-03-012318820210.1096/fba.2019-00084Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex IBettina Rieger0Sven Thierbach1Miriam Ommer2Finja S.V. Dienhart3Susanne Fetzner4Karin B. Busch5Institute of Molecular Cell Biology Faculty of Biology University of Muenster Muenster GermanyInstitute for Molecular Microbiology and Biotechnology Faculty of Biology University of Muenster Muenster GermanyInstitute of Molecular Cell Biology Faculty of Biology University of Muenster Muenster GermanyInstitute of Molecular Cell Biology Faculty of Biology University of Muenster Muenster GermanyInstitute for Molecular Microbiology and Biotechnology Faculty of Biology University of Muenster Muenster GermanyInstitute of Molecular Cell Biology Faculty of Biology University of Muenster Muenster GermanyAbstract Pseudomonas aeruginosa is a Gram‐negative bacterium of the proteobacteria class, and one of the most common causes of nosocomial infections. For example, it causes chronic pneumonia in cystic fibrosis patients. Patient sputum contains 2‐heptyl‐4‐hydroxyquinoline N‐oxide [HQNO] and Pseudomonas quorum sensing molecules such as the Pseudomonas quinolone signal [PQS]. It is known that HQNO inhibits the enzyme activity of mitochondrial and bacterial complex III at the Qi (quinone reduction) site, but the target of PQS is not known. In this work we have shown that PQS has a negative effect on mitochondrial respiration in HeLa and A549 cells. It specifically inhibits the complex I of the respiratory chain. In vitro analyses showed a partially competitive inhibition with respect to ubiquinone at the IQ site. In competing studies with Rotenone, PQS suppressed the ROS‐promoting effect of Rotenone, which is typical for a B‐type inhibitor. Prolonged incubation with PQS also had an effect on the activity of complex III.https://doi.org/10.1096/fba.2019-00084HyPer‐3IQ site inhibitionmitochondriaPseudomonas aeruginosaPseudomonas quinolone signal (PQS)Respiratory complex I
spellingShingle Bettina Rieger
Sven Thierbach
Miriam Ommer
Finja S.V. Dienhart
Susanne Fetzner
Karin B. Busch
Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex I
FASEB BioAdvances
HyPer‐3
IQ site inhibition
mitochondria
Pseudomonas aeruginosa
Pseudomonas quinolone signal (PQS)
Respiratory complex I
title Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex I
title_full Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex I
title_fullStr Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex I
title_full_unstemmed Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex I
title_short Pseudomonas Quinolone Signal molecule PQS behaves like a B Class inhibitor at the IQ site of mitochondrial complex I
title_sort pseudomonas quinolone signal molecule pqs behaves like a b class inhibitor at the iq site of mitochondrial complex i
topic HyPer‐3
IQ site inhibition
mitochondria
Pseudomonas aeruginosa
Pseudomonas quinolone signal (PQS)
Respiratory complex I
url https://doi.org/10.1096/fba.2019-00084
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