Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial Infection
Copyright © 2018 Fraser-Pitt et al..
Cysteamine is an endogenous aminothiol produced in mammalian cells as a consequence of coenzyme A metabolism through the activity of the vanin family of pantetheinase ectoenzymes. It is known to have a biological role in oxidative stress, inflammation, and cell migration. There have been several reports demonstrating anti-infective properties targeting viruses, bacteria, and even the malarial parasite. We and others have previously described broad-spectrum antimicrobial and antibiofilm activities of cysteamine. Here, we go further to demonstrate redox-dependent mechanisms of action for the compound and how its antimicrobial effects are, at least in part, due to undermining bacterial defenses against oxidative and nitrosative challenges. We demonstrate the therapeutic potentiation of antibiotic therapy against Pseudomonas aeruginosa in mouse models of infection. We also demonstrate potentiation of many different classes of antibiotics against a selection of priority antibiotic-resistant pathogens, including colistin (often considered an antibiotic of last resort), and we discuss how this endogenous antimicrobial component of innate immunity has a role in infectious disease that is beginning to be explored and is not yet fully understood.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:86 |
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| Enthalten in: |
Infection and immunity - 86(2018), 6 vom: 15. Juni |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fraser-Pitt, Douglas J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.01.2019 Date Revised 19.03.2019 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.1128/IAI.00947-17 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM282364641 |
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| 245 | 1 | 0 | |a Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial Infection |
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| 500 | |a Date Revised 19.03.2019 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Fraser-Pitt et al. | ||
| 520 | |a Cysteamine is an endogenous aminothiol produced in mammalian cells as a consequence of coenzyme A metabolism through the activity of the vanin family of pantetheinase ectoenzymes. It is known to have a biological role in oxidative stress, inflammation, and cell migration. There have been several reports demonstrating anti-infective properties targeting viruses, bacteria, and even the malarial parasite. We and others have previously described broad-spectrum antimicrobial and antibiofilm activities of cysteamine. Here, we go further to demonstrate redox-dependent mechanisms of action for the compound and how its antimicrobial effects are, at least in part, due to undermining bacterial defenses against oxidative and nitrosative challenges. We demonstrate the therapeutic potentiation of antibiotic therapy against Pseudomonas aeruginosa in mouse models of infection. We also demonstrate potentiation of many different classes of antibiotics against a selection of priority antibiotic-resistant pathogens, including colistin (often considered an antibiotic of last resort), and we discuss how this endogenous antimicrobial component of innate immunity has a role in infectious disease that is beginning to be explored and is not yet fully understood | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Pseudomonas aeruginosa | |
| 650 | 4 | |a antibiotic resistance | |
| 650 | 4 | |a antimicrobial agents | |
| 650 | 4 | |a azithromycin | |
| 650 | 4 | |a colistin | |
| 650 | 4 | |a cysteamine | |
| 650 | 4 | |a innate immunity | |
| 650 | 4 | |a nitric oxide | |
| 650 | 4 | |a reactive oxygen species | |
| 650 | 4 | |a vanin-1 | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Reactive Nitrogen Species |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Cysteamine |2 NLM | |
| 650 | 7 | |a 5UX2SD1KE2 |2 NLM | |
| 650 | 7 | |a Cystamine |2 NLM | |
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| 700 | 1 | |a Mercer, Derry K |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Kowalczuk, Aleksandra |e verfasserin |4 aut | |
| 700 | 1 | |a Robertson, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Lovie, Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Perenyi, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Cole, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Doumith, Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Hill, Robert L R |e verfasserin |4 aut | |
| 700 | 1 | |a Hopkins, Katie L |e verfasserin |4 aut | |
| 700 | 1 | |a Woodford, Neil |e verfasserin |4 aut | |
| 700 | 1 | |a O'Neil, Deborah A |e verfasserin |4 aut | |
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