Deciphering the Role of Bacterial Sphingolipids in Host-microbe Interactions

University Of Hawaii, Honolulu

Investigators

Abstract

We live in a microbial world, one in which chemical signals produced by bacteria influence the biology of neighboring organisms. Bacterial sphingolipids are a novel group of compounds that the Principal Investigator (PI) proposes to investigate as signals that can influence the development and evolution of other organisms. These studies may lead to a greater understanding of how communities of microbes, including our own, function and are maintained. The PI is committed to enhancing awareness of the role of host-microbe interactions in the broader educational and research community by integrating these concepts into undergraduate and graduate course curricula, direct mentoring of graduate and undergraduate students, and community presentations at local venues. Importantly, this proposal leverages the location of research to increase the participation of underrepresented minorities. As the major Native Hawaiian-serving institution in the nation, the University of Hawaii at Manoa provides the opportunity to involve Native Hawaiian students in targeted undergraduate research programs and K-12 outreach in STEM fields. Finally the PI will produce short online videos on host-microbe interactions accessible to general audiences in the Hawaiian language. Animals evolved in seas that swarmed with bacteria, yet the influences of bacteria on animal origins are poorly understood. Historically research on interactions between marine animals and microbes has emphasized bacterial pathogens, but bacteria interact with eukaryotes in other ways, and these interactions can affect animal evolution. Choanoflagellates are the closest living relatives to animals, and their ability to transition between single-celled and multicellular states is relevant to discussions of metazoan origins and their reliance upon bacteria as prey is relevant to discussions of host-microbe interactions. Algoriphagus machipongonensis is a bacterium that is associated with the choanoflagellate Salpingoeca rosetta, and the PI has shown that a novel sphingolipid from this bacterial species regulates multicellular development in the choanoflagellate. Sphingolipids are potent second messengers in eukaryotes, but the functions of bacterial sphingolipids are poorly understood. The discovery that bacterial sphingolipids regulate multicellular development in one of the closest living relatives of animals suggests that these compounds act as signaling molecules in bacteria as well. Three aims are proposed to address the hypothesis that sphingolipids produced by Bacteroidetes bacteria also mediate microbe-microbe signaling via membrane vesicles: (1) Identify and characterize the proteins in A. machipongonensis that are involved in bacterial sphingolipid regulation; (2) Determine and characterize how bacterial sphingolipids affect other prokaryotic cells; and (3) Define the signaling interface between bacterial sphingolipid signals and other cells. These organisms are easily maintained under laboratory conditions, and analyses will be facilitated by the availability of the genome sequences of two choanoflagellates and their prey bacteria, ease of maintaining these organisms under laboratory conditions, their amenability to biochemical and cell biological approaches, and genetic techniques developed by the PI for the bacterial partner .