Image courtesy of Jason Crawford.
Escherichia coli is a dominant bacterial member of the human intestinal tract and a major model organism in biology. Some members of E. coli contribute to a healthy gut ecosystem, whereas others are pathogens causing over a million infections worldwide that often develop antibiotic resistance. Despite this, mechanisms for regulation of its population-level phenotypes, which are associated with pathogenesis, have remained elusive. Researchers in Professor Jason Crawford’s group in the Departments of Chemistry and Microbial Pathogenesis at Yale University, however, have illuminated a key pathway underlying this phenomenon at the molecular level. They have discovered the structure and pathway of autoinducer-3 (AI-3), an uncharacterized signal responsible for regulating virulence.
This signal is secreted from the bacteria during growth, accumulating as cells divide and allowing the bacteria to assess their numbers. Researchers isolated the metabolite by applying cellular stress. Then, the structure was determined using one- and two-dimensional Nuclear Magnetic Resonance spectroscopy. Additionally, the effects of AI-3 were tested on both bacteria and human tissue. Upon introducing the metabolite to a strain of E. coli that causes intestinal lesions and kidney failure, the bacteria became more virulent. When introduced to human tissue, an inflammatory effect was observed, indicating human cells can detect and combat these signals.
The elucidation of the AI-3 structure and pathway is a crucial step forward in microbial pathogenesis. “It can be used to determine the collection of genes regulated by the AI-3 molecule in other pathogenic bacteria,” Crawford said. These findings pave the way to combatting virulence in a variety of pathogens.
Kim, Chung Sub, et al. “Characterization of Autoinducer-3 Structure and Biosynthesis in E. Coli.” ACS Central Science, vol. 6, no. 2, 2020, pp. 197–206., doi:10.1021/acscentsci.9b01076.
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