E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

Identification of suitable host conditions for the hatching of t muris t suis and t trichiura in the mucosal microbiota of pigs humans and a humanised mice model to understand the molecular basis of hatching in trichuris species (#284)

Tapoka T Mkandawire 1 , Peter L Nejsum 2 , Richard K Grencis 3 , Matthew Berriman 1 , Maria A Duque-Correa 1
  1. Parasite Genomics, Wellcome Sanger Institute, Cambridge, United Kingdom
  2. Dept of Infectious Disease, Aarhus University, Aarhus, Denmark
  3. Lydia Becker Institute Of Immunology And Inflammation, Wellcome Centre For Cell Matrix Research, School Of Biological Sciences, Faculty Of Biology, Medicine And Health, The University Of Manchester, Manchester, United Kingdom

Trichuriasis is a disease caused by infection with Trichuris trichiura, the human whipworm; affecting over 700 million people. Infection occurs upon ingestion of whipworm eggs that hatch and establish in the cecum and proximal colon. Trichuriasis has been studied in murine and porcine models, T. muris and T. suis respectively; revealing the role of the host intestinal microbiota in inducing hatching of whipworm eggs. Escherichia coli surface molecules play a role in the hatching of T. muris. We hypothesise that the same or similar molecules found in specific conformations on members of the host gut microbiota– specifically those closely associated with the intestinal mucosa, trigger hatching across other Trichuris species, through physical interaction and enzymatic activity. To understand the molecular basis of hatching across species and identify human gut microbiota capable of hatching T. trichiura we probed the interactions between E. coli and T. muris; and have identified classes proteins and proteases important to the hatching process by observing reductions in T. muris hatching. We investigated the effect on hatching of these proteases in vitro using lumenal and mucosal microbiota samples from a range of hosts including pigs, humans, and a humanised mice model. We hope to build a picture of hatching across the Trichuris species by using metagenomics, transcriptomics, and proteomics to analyse these samples which include human intestinal biopsies, porcine and humanised murine intestinal mucosal samples, purified gut microbiota, and faecal samples to search for bacteria expressing molecules key to the hatching process. Additionally, we are using these techniques to build a high throughput hatching screening platform to test and validate our candidate molecules and human gut microbiota, and can be applied to other large-scale investigations.