Title | Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Schiessl KT, Hu F, Jo J, Nazia SZ, Wang B, Price-Whelan A, Min W, Dietrich LEP |
Journal | Nat Commun |
Volume | 10 |
Issue | 1 |
Pagination | 762 |
Date Published | 2019 02 15 |
ISSN | 2041-1723 |
Keywords | Anti-Bacterial Agents, Biofilms, Ciprofloxacin, Drug Resistance, Bacterial, Phenazines, Pseudomonas aeruginosa, Spectrum Analysis, Raman |
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. |
DOI | 10.1038/s41467-019-08733-w |
Alternate Journal | Nat Commun |
PubMed ID | 30770834 |
PubMed Central ID | PMC6377615 |
Grant List | R01 AI103369 / AI / NIAID NIH HHS / United States R01 EB020892 / EB / NIBIB NIH HHS / United States T32 GM008798 / GM / NIGMS NIH HHS / United States |
Submitted by api_import on December 20, 2019 - 3:23pm