Current Research
RAM Physiology
Colorful, redox active metabolites (RAMs) are made by many different microbes. Their redox activity makes them fun to work with because they change color depending on their oxidation state. Historically overlooked as "secondary" metabolites, we have shown that phenazine RAMs play critical roles in helping Pseudomonas aeruginosa survive under stressful conditions at low power outputs, including in the cores of biofilms. Using a variety of approaches, including genetics and high-throughput electrochemistry, we continue to deepen our understanding of RAM-based maintenance metabolism; this work has direct relevance for controlling bacterial populations and communities in diverse contexts.
Related Recent Publications:
Horak, Richard A.; Ciemniecki, John A. et al. (2024) Bioenergetic suppression by redox-active metabolites promotes antibiotic tolerance in Pseudomonas aeruginosa, PNAS 121(46):e2406555121
Ciemniecik, John A.; Ho Chia-Lun; et al. (2024) Mechanistic study of a low-power maintenance state using high-throughput electrochemistry, Cell https://doi.org/10.1016/j.cell.2024.09.042 See commentary here
Typin, Lev M.Z.; Saunders, Scott H. et al. (2024) Genetically dissecting the electron transport chain of a soil bacterium reveals a generalizable mechanism for biological phenazine oxidation, PLOS Genetics May, 1011064
Meirelles, Lucas A.*.;Perry, Elena M.* et al. (2021) Bacterial defenses against a natural antibiotic promote collateral resilience to clinical antibiotics, PLOS Biology 19(3): e3001093. See commentary here
Chronic Infections
Chronic human infections cause major harm, including destroying the lungs of individuals living with cystic fibrosis and resulting in limb amputations due to wound healing failure in diabetics. Because the opportunistic pathogens causing these infections are growing slowly in hypoxic/anoxic environments, they are often physiologically tolerant to conventional antibiotics. We iterate between developing means to characterize the microenvironments in which these pathogens thrive in situ, and using reductionist in vitro approaches to understand how they do so (see section on RAM Physiology) to develop novel therapeutic approaches.
Related Recent Publications:
Wang, Renee Z.; Lonergan, Zachery R. et al. (2024) Widespread detoxifying NO reductases impart a distinct isotopic fingerprint on N2O under anoxia, PNAS, 121 (25): e2319960121.
Kim, Jane H.; Spero, Melanie; et al. (2024) Targeting anaerobic respiration in Pseudomonas aeruginosa with chlorate improves the healing of chronic wounds, Advances in Wound Care, 13(2): 53-69.
Wilbert, Steven A. and Newman, Dianne K. (2022) The contrasting roles of nitric oxide drive microbial community organization as a function of oxygen presence, Current Biology, 32(24): 5221-5234. See commentary here
Dar, Daniel; Dar, Nina et al. (2021) Spatial transcriptomics of planktonic and sessile bacterial populations at single-cell resolution, Science; 373(6556): eabi4882. See commentary here
Rhizosphere Studies
In 1962, Rachel Carson wrote in Silent Spring: "There are few studies more fascinating, and at the same time more neglected, than those of the teeming populations that exist in the dark realms of the soil. We know too little of the threads that bind the soil microorganisms to each other and to their world, and to the world above." These words are more resonant today than ever, especially in the context of climate change and the critical role soil plays in carbon cycling and food security. Accordingly, we have begun to study phenazine-based microbial community interactions in diverse rhizospheres, testing the hypothesis that phenazines are "keystone metabolites".
Related Recent Publications:
Zhang, Oumeng*; Alcalde, Reinaldo E*.; et al. (2024) Investigating 3D microbial community dynamics of the rhizosphere using quantitative phase and fluorescence microscopy, PNAS, 121 (33): e2403122121. See commentary here and highlight here
McRose, Darcy L.; Li, J. et al. (2023) The chemical ecology of coumarins and phenazines affects iron acquisition by pseudomonads, PNAS, 120 (14): e2217951120. See commentary here
McRose, Darcy L. & Newman, Dianne K. (2021) Redox-active antibiotics enhance phosphorous bioavailability, Science; 371:1033-1037. See commentary here
Dahlstrom, Kurt M.; McRose, Darcy L. et al. (2020) Keystone metabolites of crop rhizosphere microbiomes, Current Biology, 30(19):R1131–R1137.