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

Cysteamine is an endogenous aminothiol produced in mammalian cells as 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 activity of cysteamine. Here we go further to demonstrate REDOX dependent mechanisms of action for this compound and how its antimicrobial effects are at least in part due to undermining bacterial defenses to oxidative and nitrosative challenge. We demonstrate the therapeutic potentiation of antibiotic therapy against P. aeruginosa in mouse models of infection. We also demonstrate potentiation of many different classes of antibiotic 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 which is beginning to be explored and is not yet fully understood.