Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms

Konstanze T. Schiessl, Fanghao Hu, Jeanyoung Jo, Sakila Z. Nazia, Bryan Wang, Alexa Price-Whelan, Wei Min () and Lars E. P. Dietrich ()
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Konstanze T. Schiessl: Columbia University
Fanghao Hu: Columbia University
Jeanyoung Jo: Columbia University
Sakila Z. Nazia: Columbia University
Bryan Wang: Columbia University
Alexa Price-Whelan: Columbia University
Wei Min: Columbia University
Lars E. P. Dietrich: Columbia University

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Antibiotic efficacy can be antagonized by bioactive metabolites and other drugs present at infection sites. Pseudomonas aeruginosa, a common cause of biofilm-based infections, releases metabolites called phenazines that accept electrons to support cellular redox balancing. Here, we find that phenazines promote tolerance to clinically relevant antibiotics, such as ciprofloxacin, in P. aeruginosa biofilms and that this effect depends on the carbon source provided for growth. We couple stable isotope labeling with stimulated Raman scattering microscopy to visualize biofilm metabolic activity in situ. This approach shows that phenazines promote metabolism in microaerobic biofilm regions and influence metabolic responses to ciprofloxacin treatment. Consistent with roles of specific respiratory complexes in supporting phenazine utilization in biofilms, phenazine-dependent survival on ciprofloxacin is diminished in mutants lacking these enzymes. Our work introduces a technique for the chemical imaging of biosynthetic activity in biofilms and highlights complex interactions between bacterial products, their effects on biofilm metabolism, and the antibiotics we use to treat infections.

Date: 2019
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DOI: 10.1038/s41467-019-08733-w

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