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Redox metabolite role in biofilms
In the microbial world, the chemical diversity of secreted metabolites is vast, and their physiological roles are underexplored. Costa et al. studied the redox-active secondary metabolite pyocyanin, which is produced by the opportunistic pathogen Pseudomonas aeruginosa. Pyocyanin mediates the generation of thick biofilms containing extracellular DNA that are important in pathogenesis. The authors characterized the demethylase PodA, which catalyzes the conversion of pyocyanin to hydroxyphenazine and deranges biofilm formation. PodA could represent a therapeutic lead for intractable bacterial infections.
Science, this issue p. 170
Abstract
The opportunistic pathogen Pseudomonas aeruginosa produces colorful redox-active metabolites called phenazines, which underpin biofilm development, virulence, and clinical outcomes. Although phenazines exist in many forms, the best studied is pyocyanin. Here, we describe pyocyanin demethylase (PodA), a hitherto uncharacterized protein that oxidizes the pyocyanin methyl group to formaldehyde and reduces the pyrazine ring via an unusual tautomerizing demethylation reaction. Treatment with PodA disrupts P. aeruginosa biofilm formation similarly to DNase, suggesting interference with the pyocyanin-dependent release of extracellular DNA into the matrix. PodA-dependent pyocyanin demethylation also restricts established biofilm aggregate populations experiencing anoxic conditions. Together, these results show that modulating extracellular redox-active metabolites can influence the fitness of a biofilm-forming microorganism.
