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The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development
Open accessAbstract
Significance: Efflux-based drug resistance complicates the treatment of infectious diseases and cancers. Cellular exposure to ecological toxins or reactive metabolites may influence the conservation and activity of efflux pumps. Yet, for most such systems, we know very little about their natural substrates and the signals controlling pump expression. Using diverse approaches, including a chip-based method of electrochemical detection, we show that the endogenous and reactive antibiotic 5-methylphenazine-1-carboxylate (5-Me-PCA) is transported by the efflux pump MexGHI-OpmD in Pseudomonas aeruginosa . Furthermore, we demonstrate that 5-Me-PCA activates expression of its cognate transporter and that it is required for normal P. aeruginosa biofilm morphogenesis. Our results provide insight into mechanisms of self-resistance and determinants of multicellular behavior in this major cause of biofilm-based infections.
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Cites
Bacterial community morphogenesis is intimately linked to the intracellular redox state
Dietrich, L. E. P., Okegbe, C., Price-Whelan, A., Sakhtah, H., Hunter, R. C., & Newman, D. K. (2013) · Journal of Bacteriology · doi:10.1128/jb.02273-12 · Cited by 291
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Towards robust Pseudomonas cell factories to harbour novel biosynthetic pathways
Bitzenhofer, N. L., Kruse, L., Thies, S., Wynands, B., Lechtenberg, T., Rönitz, J., Kozaeva, E., Wirth, N. T., Eberlein, C., Jaeger, K.-E., et al. (2021) · Essays in Biochemistry · doi:10.1042/ebc20200173 · Cited by 75
Metadata
- Authors
- Sakhtah, H., Koyama, L., Zhang, Y., Morales, D. K., Fields, B. L., Price-Whelan, A., Hogan, D. A., Shepard, K., & Dietrich, L. E. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2016-06-06
- Volume
- 113
- Issue
- 25
- Pages
- E3538-47
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2416085361
- Cited by
- 167
- References
- 1
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development. https://app.cochat.ai/papers/10.1073/pnas.1600424113
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- Sakhtah, H., Koyama, L., Zhang, Y., Morales, D. K., Fields, B. L., Price-Whelan, A., Hogan, D. A., Shepard, K., & Dietrich, L. E. P. (2016). The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1600424113
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