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Investigations of bacterial natural products in microbe-microbe interactions

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2025-02-18

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Wong, Joel Wen Han. 2025. Investigations of Bacterial Natural Products in Microbe-Microbe Interactions. Doctoral Dissertation, Harvard University Graduate School of Arts and Sciences.

Abstract

Bacteria are prolific producers of natural products, diverse secondary metabolites that can play crucial roles in their survival, interactions, and environmental adaptation. While many natural products have been harnessed to treat human diseases, their ecological functions in natural environments are often overlooked and poorly understood. In complex microbial communities encompassing bacteria, fungi, and viruses, natural products shape microbial interactions and ecosystem dynamics, with potential implications for host homeostasis. An understanding of their functions and downstream impact may inform new strategies for manipulating microbial communities in medical, agricultural, and environmental applications. This dissertation documents our efforts to advance our understanding of the ecological roles of colibactin, a genotoxin produced by strains of Escherichia coli found in the human gut. It also reveals a newly discovered function for aryl polyenes, a highly abundant class of Gram-negative bacterial natural products. These investigations have revealed unprecedented roles for these compounds and their influence on the viruses that infect bacteria (bacteriophages), offering new perspectives on the chemical language that shapes microbial communities.

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colibactin, ecology, natural products, phages, Chemistry

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