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Infect Immun. 2018 May 22;86(6). pii: e00947-17. doi: 10.1128/IAI.00947-17. Print 2018 Jun.

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.

Author information

1
NovaBiotics Ltd., Craibstone, Aberdeen, United Kingdom doug@novabiotics.co.uk.
2
NovaBiotics Ltd., Craibstone, Aberdeen, United Kingdom.
3
Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, United Kingdom.

Abstract

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.

KEYWORDS:

Pseudomonas aeruginosa; antibiotic resistance; antimicrobial agents; azithromycin; colistin; cysteamine; innate immunity; nitric oxide; reactive oxygen species; vanin-1

PMID:
29581193
PMCID:
PMC5964511
DOI:
10.1128/IAI.00947-17
[Indexed for MEDLINE]
Free PMC Article

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