Enzymatic Degradation of Pyocyanin Blocks Pseudomonas Biofilm Formation

An enzyme isolated from the soil bacterium Mycobacterium fortuitum was found to prevent biofilm formation by the aggressively pathogenic Gram-negative bacterium Pseudomonas aeruginosa.

P. aeruginosa biofilms can develop as chronic opportunistic infections, which are a serious problem for medical care, especially for immunocompromised patients and the elderly. Biofilms often cannot be treated effectively with traditional antibiotic therapy, as they seem to protect bacteria from adverse environmental factors.

Pyocyanin is one of the many toxins produced and secreted by P. aeruginosa. It is a blue, secondary metabolite with the ability to oxidize and reduce other molecules and therefore can kill microbes competing against P. aeruginosa as well as mammalian cells of the lungs, which P. aeruginosa has infected during cystic fibrosis.

Investigators at the California Institute of Technology (Pasadena, USA) and the University of Oxford (United Kingdom) described in the December 8, 2016, online edition of the journal Science the discovery of an enzyme isolated from Mycobacterium fortuitum that oxidized the pyocyanin methyl group to formaldehyde and reduced the pyrazine ring via an unusual tautomerizing demethylation reaction.

Treatment of P. aeruginosa with this pyocyanin demethylase (PodA) enzyme disrupted biofilm formation.

"Pseudomonas aeruginosa causes chronic infections that are difficult to treat, such as those that inhabit burn wounds, diabetic ulcers, and the lungs of individuals living with cystic fibrosis," said senior author Dr. Dianne Newman, professor of biology and geobiology at the California Institute of Technology. "In part, the reason these infections are hard to treat is because P. aeruginosa enters a biofilm mode of growth in these contexts; biofilms tolerate conventional antibiotics much better than other modes of bacterial growth. Our research suggests a new approach to inhibiting P. aeruginosa biofilms."

"What is interesting about this result from an ecological perspective is that a potential new therapeutic approach comes from leveraging reactions catalyzed by soil bacteria," said Dr. Newman. "These organisms likely co-evolved with the pathogen, and we may simply be harnessing strategies other microbes use to keep it in check in nature. The chemical dynamics between microorganisms are fascinating, and we have so much more to learn before we can best exploit them."

Related Links:
California Institute of Technology
University of Oxford