Antimicrobial properties of pyridine-2,6-dithiocarboxylic acid, a metal chelator produced by Pseudomonas spp.

Pyridine-2,6-dithiocarboxylic acid (pdtc) is a metal chelator produced by P seudomonas spp. It has been shown to be involved in the biodegradation of c arbon tetrachloride; however, little is known about its biological function . In this study, we examined the antimicrobial properties of pdtc and the m echanism of its antibiotic activity. The growth of Pseudomonas stutzeri str ain KC, a pdtc-producing strain, was significantly enhanced by 32 muM pdtc. All nonpseudomonads and two strains of P. stutzeri were sensitive to 16 to 32 muM pdtc. In general, fluorescent pseudomonads were resistant to all co ncentrations tested. In competition experiments, strain KC demonstrated ant agonism toward Escherichia coli. This effect was partially alleviated by 10 0 muM FeCl3. Less antagonism was observed in mutant derivatives of strain K C (CTN1 and KC657) which lack the ability to produce pdtc. A competitive ad vantage was restored to strain CTN1 by cosmid pT31, which restores pdtc pro duction. pT31 also enhanced the pdtc resistance of all pdtc-sensitive strai ns, indicating that this plasmid contains elements responsible for resistan ce to pdtc. The antimicrobial effect of pdtc was reduced by the addition of Fe(III), Co(III), and Cu(II) and enhanced by Zn(II). Analyses by mass spec trometry determined that Cu(I):pdtc and Co(III):pdtc(2) form immediately un der our experimental conditions. Our results suggest that pdtc is an antago nist and that metal sequestration is the primary mechanism of its antimicro bial activity. It is also possible that Zn(II), if present, may play a role in pdtc toxicity.