Transcriptomic profiling suggests that promysalin alters metabolic flux, motility, and iron regulation in Pseudomonas putida KT2440

Authors: GIGLIO, KRISTA - Former ARS Employee; KEOHANE, COLLEEN - Emory University; Stodghill, Paul; STEELE, ANDREW - Emory University; FETZER, CHRISTIAN - Technische Universitat Munchen; SIEBER, STEPHEN - Technische Universitat Munchen; Filiatrault, Melanie; WUEST, WILLIAM - Emory University

Submitted to: ACS Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/25/2018
Publication Date: 5/25/2018
Citation: Giglio, K., Keohane, C.E., Stodghill, P., Steele, A.D., Fetzer, C., Sieber, S., Filiatrault, M.J., Wuest, W.M. 2018. Transcriptomic profiling suggests that promysalin alters metabolic flux, motility, and iron regulation in Pseudomonas putida KT2440. ACS Infectious Diseases. https://doi.org/10.1021/acsinfecdis.8b00041.
DOI: https://doi.org/10.1021/acsinfecdis.8b00041

Interpretive Summary: Promysalin was recently discovered as a natural product produced by the bacterium Pseudomonas putida strain RW10S1. The natural product is able to inhibit growth of some bacteria, and promote surface motility in other bacteria. To determine the mechanism of how the compound promotes surface motility we grew bacteria in the presence and absence of the compound and analyzed global changes in gene expression. We found that the genes involved in motility as well as iron acquisition and storage are generally down regulated in bacterial cells treated with the compound. Our data also indicate that treatment with the compound induces a shift in bacterial metabolism. Overall, these data provide insight in the mechanism of action of the compound produced by Pseudomonas putida and suggests cells treated with promysalin experience iron-limited growth conditions.

Technical Abstract: Promysalin, a secondary metabolite produced by P. putida RW10S1, is a narrow-spectrum antibiotic that targets P. aeruginosa over other Pseudomonas spp. P. putida KT2440, a non-producing strain, displays increased swarming motility and decreased pyoverdine production in the presence of exogenous promysalin. Herein, proteomic and transcriptomic experiments were used to provide insight about how promysalin elicits responses in PPKT2440 and rationalize its species-selectivity. RNA-sequencing results suggest that promysalin affects PPKT2440 by 1) increasing swarming in a flagella-independent manner; 2) causing cells to behave as if they were experiencing an iron-deficient environment, and 3) shifting metabolism away from glucose conversion to pyruvate via the Entner- Doudoroff pathway. These findings highlight Nature’s ability to develop small molecules with specific targets that result in exquisite selectivity.