Pyrithione biocides as inhibitors of bacterial ATP synthesis

Abstract

LI E R. 1998. Sodium pyrithione and zinc pyrithione (NaPT and ZnPT, respectively) are widely used as cosmetic preservatives and general antimicrobial agents. They have been shown to be active against fungal cell walls, associated membranes and bacterial transport processes. Investigations were undertaken into the effect of these antimicrobial agents on substrate catabolism and intracellular ATP levels using an oxygen electrode and luciferin-luciferase technology, respectively. Results indicate that, while both compounds are poor inhibitors of substrate catabolism, sub-inhibitory concentrations of biocide greatly reduces intracellular ATP levels in both Escherichia coli NCIMB 10000 and Pseudomonas aeruginosa NCIMB 10548. This is thought to be due to the action of NaPT and ZnPT on the Gram-negative bacterial membrane. INTRODUCTIONSodium pyrithione and zinc pyrithione (NaPT and ZnPT, respectively, Fig. 1) are the sodium salt and zinc chelate of 1-hydroxy-2-pyridinethiol (Shaw et al. 1950 ;Albert et al. 1956 ;Hyde and Nelson 1984). Both NaPT and ZnPT have been shown to possess a wide spectrum of antimicrobial activity against fungal and bacterial species (Pansy et al. 1953 ;Albert et al. 1956 ;Hyde and Nelson 1984 ;Khattar et al. 1988). They are widely used as cosmetic preservatives (Nelson and Hyde 1981 ;Hyde and Nelson 1984) and are incorporated as anti-dandruff agents in shampoos (Fredriksin and Feargeman 1983 ;Hyde and Nelson 1984). They also possess excellent metal chelating properties and ZnPT is active as a metal complex (Davies 1985 ;Fenn and Alexander 1988).Previous work has suggested that this group of compounds is membrane active. This is indicated by the inhibition of uptake of several unrelated substrates in both bacteria and fungi (Chandler and Segel 1978;Friedman 1981;Khattar et al. 1988 ;Khattar and Salt 1993) and the observed depolarization of the transmembrane electrical potential in Neurospora crassa (Ermolayeva et al. 1995). The effects of an antimicrobial agent on substrate transport and related metabolism may be used as indicators of the membrane activity of the test agent (Gilbert et al. 1991). In turn, these effects may be reflected as a reduction in intracellular ATP levels (Harold Dundee, Bell Street, Dundee, DD1 1HG,.© 1998 The Society for Applied Microbiology 1972). Regardless of substrate transport, a direct membrane effect by a biocide may decrease intracellular ATP levels via disruption of the transmembrane proton motive force (PMF) and related processes. This has been exhibited with several membrane active agents including fentichlor, PHMB, alexidine and chlorhexidine (Bloomfield 1974 ;Chopra et al. 1987 ;Chawner and Gilbert 1989).This study describes the activity of NaPT and ZnPT on substrate transport and catabolism in Escherichia coli NCIMB 10000 and Pseudomonas aeruginosa NCIMB 10548 and the effects of these agents on bacterial intracellular ATP levels at sub-inhibitory and minimal inhibitory concentrations (MIC). MATERIALS AND METHODS Organisms and chemicalsStock cultures of Es...

Antimicrobial Performance of Thermoplastic Elastomers Containing Zinc Pyrithione and Silver Nanoparticles

“…The differential effectiveness observed between the additives tested herein may be related to the way in which these metals operate. Nanosilver is positively charged and bacterial cell wall is negative, which leads to an electrical disturbance; pyrithione is a chelating agent that can sequestrate metal ions which are important in bacterial cell conformation 7 . This property also causes an electrical disorder in bacteria membranes, mainly Gram-negative ones, due to the action on lipopolysaccharide groups, present in the outer membrane of these microorganisms 33 .…”

“…Previous studies report that pyrithione can penetrate bacterial cytosol besides acting in cell membrane 32 . Once inside the cell, the chelating mechanism of ZnPT promotes a disorder in the cell envelope, owing to the leakage of intracellular components as well as the inhibition of nutrient uptake 7 . In the present investigation, metal uptake by bacteria was not explored.…”

“…Among organic additives, 5-chloro-2-(2,4-dichlorophenoxy) phenol (Triclosan ® ), isothiazolone and zinc pyrithione (ZnPT) have shown efficacy and fast results toward a large range of microorganisms, such as Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Salmonella choleraesuis and Staphylococcus aureus 6 . The industrial use of ZnPT is more common as anti-dandruff in shampoo and soap, and in body wash due to its low water solubility, lack of color and odor when applied in cosmetics [7][8][9] . As antifungal and antibacterial, this substance has been used in paints 10 , textiles 11 and polymeric matrices as polyurethane foam 6 and polyvinyl chloride (PVC) 12 .…”

Pyrithione biocide interactions with bacterial phospholipid head groups

“…The tube dilution technique (Bloomfield 1991) was utilized to determine the effect of potential neutralizers (D-cysteine, D-alanine, EDTA, phosphatidylcholine, phosphatidylethanolamine, linoleic acid and L-glucose) on the minimum inhibitory concentration (MIC) values of both NaPT and ZnPT (Dinning et al 1998). The potential neutralizers were chosen as representative compounds from each major group of biologically active compounds.…”

“…In bacteria, the inhibition of thymidine and uracil transport processes has been reported (Khattar et al 1988(Khattar et al , 1989. Previous work performed in this laboratory suggests that both pyrithiones induce the leakage of intracellular material from exposed cultures of Escherichia coli and Pseudomonas aeruginosa as well as affecting nutrient uptake in bacteria by the inhibition of membrane-bound metabolic processes (Dinning et al 1998).…”