Collaborative Research: OSIB: Chemical signaling in a host-microbe symbiosis

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

Despite an appreciation of the importance of symbiotic microbes, the chemical language used between hosts and microorganisms is poorly understood. There is a current gap in knowledge when it comes to the expressed chemistry that bacteria utilize to adapt to host environments, and the identification of the chemical matter responsible would add significantly to our understanding of how bacteria are able to colonize and maintain themselves in niche environments or out-compete other microorganisms for the same niche. Our proposal is highly interdisciplinary, as is our team, incorporating forward genetics, cutting-edge analytical measurement science, and medicinal chemistry to identify how the glowing bacterium, Vibrio fischeri, uses a small chemical compound to better colonize its squid host while also discovering other molecules that have yet to be identified. Our system thus provides an entry point to identify chemical signals that may be relevant in other beneficial and pathogenic colonization systems and to elucidate the relevant targets in an accessible model. We will leverage our tractable, environmentally intriguing model system to create a hands-on outreach workshop with young girls in grades 5-10 in the greater Monterey Bay area, which has a high Latinx population, in collaboration with Expanding Your Horizons. There is significant interest in identifying and characterizing small molecules that underlie host-microbe communication in plant, animal, and human host-microbiome interactions. The naturally simple association between Euprymna scolopes bobtail squid and Vibrio fischeri luminescent bacteria provides a symbiotic relationship that can be interrogated in situ to discover functional compounds. Bacterial colonization of the host is accessible to sophisticated bacterial genetic and genomic approaches, and the site of infection can be imaged in live animals. Our collaborative efforts have developed novel methods to identify and study small molecules in this symbiosis. This work has resulted in the identification of a small organic molecule, termed diketopiperazine (DKP), as a potential contributor to symbiotic biofilm and luminescence phenotypes from V. fischeri. We have used imaging mass spectrometry to identify additional biofilm-associated molecules, and, using structure elucidation and synthetic chemistry, we have synthesized large amounts of the DKP. Here, we will leverage our interdisciplinary expertise in imaging mass spectrometry, structure isolation and elucidation, forward genetic screening, and synthetic bioorganic chemistry to identify the function of this DKP and identify the biosynthetic origin of this molecule to explore whether it is used in other microbial-host systems. This model system will allow us to address current knowledge gaps in our understanding of the small molecules that symbiotic bacteria produce during colonization of host specific tissues. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.