The antibacterial mechanism of action of piroctone olamine against Staphylococcus aureus: effects on metal deprivation and membrane integrity

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Piroctone olamine (PO) is an active antifungal and antibacterial ingredient in a number of commercially important P&G formulations, including the globally successful Head & Shoulders (H&S) and Safeguard brands. Despite the recognised value of its functionality, the mechanism of action of PO is complex and poorly understood. Molecular modelling simulations carried out by P&G and at Durham suggest that the active piroctone component has the capacity to traverse bacterial membranes and exert intracellular effects. There are also indications that it can aggregate at the membrane and disrupt lipid bilayer integrity. Piroctone, the metal binding unit of PO, is a cyclic hydroxamate that resembles the constituent binding units of the siderophore desferrioxamine, which binds Fe(III) with high affinity. Indeed, multiple lines of evidence from our partnership with P&G point to a role for PO in depriving Gram-negative Escherichia coli of essential iron. However, nothing is known concerning how PO functions as an antibacterial agent against Staphylococcus aureus, a Gram-positive whose elimination is highly desirable in P&G products. S. aureus is one of six bacterial pathogens from the so-called 'ESKAPE' group that are notable for multidrug resistance and virulence. S. aureus is a common cause of nosocomial infections and there is an urgent need to develop alternative therapeutics to combat disease. Hence, in addition to the clear benefits for consumer goods with antimicrobial properties, a better understanding of the mode of action of PO will aid in evaluation of its inherent antimicrobial properties and as a potential adjuvant for other antibacterial agents. This project aims to determine the antimicrobial mode of action of PO against S. aureus and evaluate its efficacy in tandem with chelants and other ingredients routinely employed in P&G products. Information uncovered on the mode of action by restriction of metal availability or membrane disruption will allow the development of improved formulations.