NLM IRP Seminar Schedule

Abstract:

Heme degradation is an essential function in mammals, involving multiple steps performed by enzymes from both the host organism and the organism’s microbiome. During this degradation process the metabolite bilirubin is produced which can either be reabsorbed into the body leading to the development of jaundice, or can be further reduced and excreted as water soluble urobilinogen and stercobilinogen. While the gut microbiome has already been determined to be responsible for the reduction of bilirubin in the gut, the gene responsible has yet to be identified and only a few species have been determined to be bilirubin reducers. In this project we worked toward the identification and analysis of a novel bilirubin reductase enzyme. First we used comparative genomics approaches to identify potential bilirubin reductase gene candidates in bilirubin reducing bacterial strains. A putative bilirubin reductase gene was identified and experimentally confirmed to be able to reduce bilirubin in vitro. Using these confirmed genes we characterized the presence and absence of bilirubin reductase across different bacterial taxa. We then performed an analysis of infant gut metagenomes and metagenomes from IBD patients to assess the presence of these genes during development of the gut microbiome and during disease. Lastly we performed an analysis of the predicted structure of the bilirubin reductase enzyme and analyzed the sequence conservation within the putative bilirubin reductase genes to identify key residues that may be involved in the reduction reaction. Understanding what genes and bacteria are responsible for bilirubin reduction can help us understand this process more completely and develop new approaches to treating jaundice in infants.