Studies on the mode of action of the pyrithione biocides

Sodium and zinc pyrithiones (NaPT and ZnPT respectively) are inhibitors of both pathogenic fungi and bacteria and are widely used in the cosmetics industry as preservatives. However, little is known of their mode of action. Growth inhibitory data exhibited NaPT to be a poorer growth inhibitor of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> than ZnPT. A <i>Pseudomonas</i>-gap was observed between <i>E. coli</i> and <i>P. aeruginosa</i> upon their exposure to ZnPT. The antimicrobial action of these compounds was neutralised by the presence of EDTA and extracellular phosphatidylethanolamine. ZnPT was also neutralised by the presence of cysteine. Molecular modelling studies indicated direct chemical interactions between the pyrithiones and cysteine and the pyrithiones and phosphatidylethanolamine. Oxygen electrode studies exhibited low levels of pyrithione induced inhibition of substrate metabolism for several substrates in both <i>E. coli</i> and <i>P. aeruginosa</i>. The most sensitive metabolism towards the pyrithiones was that for thymidine, which exhibited inhibition to about 30% of the rate of metabolism in the control. At pyrithione concentrations approaching the MIC, the exposure of <i>E. coli</i> and <i>P. aeruginosa</i> to both biocides was shown to increase inhibited substrate metabolism for acetate, thymidine and uracil. ATP metabolism indicated extreme sensitivity to both NaPT and ZnPT in both <i>E. coli</i> and <i>P. aeruginosa</i>. The membrane effect of the pyrithiones were investigated by observing leakage of potassium ions and E260nm absorbing material from exposed cells of <i>E. coli</i> and <i>P. aeruginosa</i>. Although NaPT and ZnPT did not induce observable leakage of potassium ions from <i>E. coli</i> or <i>P. aeruginosa</i> it was found that leakage of 260nm material occurs and suggests that the leakage of potassium ions is being masked by some other event. Transmission electron microscopy indicated a disrupted bacterial envelope after exposure of <i>P. aeruginosa</i> to NaPT. Coagulation of the cytosol in proximity to the envelope was also observed. Both NaPT and ZnPT were observed to be present in the bacterial cytosol after assaying and ZnPT was observed in the envelope of <i>P. aeruginosa</i>. These results suggest that the pyrithione antimicrobial agents are mainly membrane active agents which enter the cytosol via membrane disruption where they may chelate intracellular metal cations and metalloenzymes.

Name dc:type.qualificationname

PhD

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

University of Abertay Dundee

Year dc:date.issued

1995

Author dc:creator

• Dinning, Anthony

Advisor dc:contributor.advisor

• Collier, Phillip

Language dc:language

eng

Identifier

oai:rke.abertay.ac.uk:studenttheses/cc01755b-ab34-46e1-86b6-f1ee54b0b31d

OAI identifier oai:identifier

oai:rke.abertay.ac.uk:studenttheses/cc01755b-ab34-46e1-86b6-f1ee54b0b31d