The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms
Open accessAbstract
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.
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“In hypoxic or anoxic regions, endogenous phenazines shuttle electrons to sustain adenosine triphosphate (ATP) production. This redox cycling supports fitness under low oxygen conditions and contributes directly to antibiotic resistance [48,49,50].”
From Understanding Pseudomonas aeruginosa Biofilms: Quorum Sensing, c-di-GMP Signaling, and Emerging Antibiofilm Approaches (2026) · doi:10.3390/microorganisms14010109 · cites this paper as [50]
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1 retracted
Hunter, R. C., Klepac-Ceraj, V., Lorenzi, M. M., Grotzinger, H., Martin, T. R., & Newman, D. K. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0088oc · Cited by 168
RetractedFiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
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Antibiotic resistance of bacterial biofilms
Høiby, N., Bjarnsholt, T., Givskov, M., Molin, S., & Ciofu, O. (2010) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2009.12.011 · Cited by 3,225
Synergy, antagonism, and what the chequerboard puts between them
Odds, F. C. (2003) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg301 · Cited by 2,481
Physiological heterogeneity in biofilms
Stewart, P. S., & Franklin, M. J. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1838 · Cited by 2,327
Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy
Freudiger, C. W., Min, W., Saar, B. G., Lu, S., Holtom, G. R., He, C., Tsai, J. C., Kang, J. X., & Xie, X. S. (2008) · Science · doi:10.1126/science.1165758 · Cited by 2,255
Self-citationMetabolite-enabled eradication of bacterial persisters by aminoglycosides
Allison, K. R., Brynildsen, M. P., & Collins, J. J. (2011) · Nature · doi:10.1038/nature10069 · Cited by 1,025
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Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine
Cheng, J.-X., & Xie, X. S. (2015) · Science · doi:10.1126/science.aaa8870 · Cited by 874
Cited by
Biological imaging of chemical bonds by stimulated Raman scattering microscopy
Hu, F., Shi, L., & Min, W. (2019) · Nature Methods · doi:10.1038/s41592-019-0538-0 · Cited by 392
Self-citationSaunders, S. H., Tse, E. C. M., Yates, M. D., Otero, F. J., Trammell, S. A., Stemp, E. D. A., Barton, J. K., Tender, L. M., & Newman, D. K. (2020) · Cell · doi:10.1016/j.cell.2020.07.006 · Cited by 328
Gradients and consequences of heterogeneity in biofilms
Jo, J., Price-Whelan, A., & Dietrich, L. E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00692-2 · Cited by 319
Self-citationExploring Iron Withholding by the Innate Immune Protein Human Calprotectin
Zygiel, E. M., & Nolan, E. M. (2019) · Accounts of Chemical Research · doi:10.1021/acs.accounts.9b00250 · Cited by 34
Elbehiry, A., Marzouk, E., Edrees, H. M., Ibrahem, M., Alzahrani, S., Anagreyyah, S., Abualola, H., Alghamdi, A., Alzahrani, A., Jaber, M., et al. (2026) · Microorganisms · doi:10.3390/microorganisms14010109 · Cited by 34
Metadata
- Authors
- Schiessl, K. T., Hu, F., Jo, J., Nazia, S. Z., Wang, B., Price-Whelan, A., Min, W., & Dietrich, L. E. P.
- Venue
- Nature Communications
- Published
- 2019-02-15
- Volume
- 10
- Issue
- 1
- Pages
- 762-762
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2912289068
- Cited by
- 258
- References
- 55
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- gold
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- Schiessl, K. T., Hu, F., Jo, J., Nazia, S. Z., Wang, B., Price-Whelan, A., Min, W., & Dietrich, L. E. P. (2019). Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms. Nature Communications. https://doi.org/10.1038/s41467-019-08733-w
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