Science 355, 170–173 (2017)

Credit: AAAS

Phenazines are redox-active metabolites produced by Pseudomonas aeruginosa to control virulence. While toxic to other cells, phenazines support extracellular electron transfer that promotes survival of the producer in anoxic conditions, facilitating biofilm development. In defining strategies to manipulate phenazine levels to control biofilm formation, Costa et al. characterized a Mycobacterium fortuitum enzyme, PodA, that catalyzes pyocyanin degradation via specific demethylation of N-methylated phenazines. Unlike typical demethylases, the mechanism of PodA does not proceed by electron transfer to a flavin cofactor or an iron–sulfur cluster during oxidation of the pyocyanin methyl group to formaldehyde. Instead, under anoxic conditions, PodA forms a reduced phenazine, and the substrate serves as the electron acceptor, which the authors verified by X-ray crystallography. The authors also tested their mechanistic model through mutagenesis of putative acid and base residues within PodA. Application of PodA could reduce formation of P. aeruginosa biofilms, presumably via metabolism of pyocyanin, which has a known role in driving release of extracellular DNA for the construction of biofilms. PodA also decreased anoxic fitness in biofilms by disrupting pyocyanin-dependent electron shuttling to oxygen. Manipulation of extracellular electron shuttles may be a viable strategy for controlling pathogenic biofilms.