Title: Mucin degradation by prevalent gastrointestinal human pathogens
Funder: The Academy of Medical Sciences

Abstract: The overall aim of the work is to characterise the mucin degrading systems in prevalent human pathogens through a combination of transcriptomics, structural, and biochemical characterisation techniques. This project will cover Clostridium perfringens, Salmonella enterica, Tannerella forsythia, and Clostridioides difficile, which will pave the way for designing new options in preventing and treating infections, exploring other pathogens, and further exploring these systems. Bacterial infections of the gastrointestinal (GI) tract are common all over the world. The sources of these infections can be from contaminated or undercooked food, untreated water, and poor sanitation. Enteric infections are also frequent secondary illnesses in individuals that have received antibiotic treatment. Compounding these issues is the increasing prevalence of multi-drug resistance. My research focusses on the degradation of the mucosal surface of the GI tract by prominent commensal and pathogenic bacteria. Some commensal bacterial species have evolved to graze on the O-glycans in mucin and this is a normal part of the important host-microbe mutualist relationship. I recently made a ground-breaking discovery by characterising key enzymes used by commensal bacteria to hydrolyse O-glycans to use as a nutrient source. Bioinformatics analysis and preliminary biochemical data indicate that these enzymes are present in pathogens associated with infections of the GI tract. Characterisation of these systems will provide alternative and adjunct therapies, such as inhibitors and pre/probiotics, which will be vital in dealing with pathogens that are becoming increasingly resistant to current treatments.

Lay abstract: There are more bacteria in a person’s gut than there are stars in our galaxy. It is the densest ecosystem on the planet. These microorganisms are collectively known as the human gut microbiota and we have a mutualistic relationship with them; we provide them with nutrients and they contribute to our health throughout our lives. The proportions of species in our gut is influenced by our diet and they influence the development and prognosis of many diseases. Gastrointestinal infections by enteric pathogens affect over 1.7 billion people annually and out of these 2.2 million of these people will die as a result. They are responsible for 1 in 9 child deaths worldwide, affecting 2,195 children every day, which is greater than AIDS, malaria, and measles altogether. This is a particularly acute issue in developing countries where access to clean water, sanitation, and hygiene is not universal. At the other end of the spectrum, in more developed countries, rates of gastrointestinal infections are much lower and usually associated with nosocomial or localised outbreaks. Issues like multidrug resistance, however, are making the spread and treatment of infections more difficult in all settings. My research will determine how common human microbial pathogens degrade the mucus layer of the GI tract. Understanding how pathogens breakdown the mucus will lead to new options in preventing and treating infections. I recently made an important discovery about how commensal microbes degrade mucus and my data indicate similar processes occur in pathogens, which I will define.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION