Dissemination of bacteria with antibiotic resistance is increasing worldwide, a trend also documented for the pathogenic bacteria Haemophilus influenzae. This represents a threat to current empirical medical treatment. Integrative and conjugative elements (ICEs) are self-transmissible mobile genetic elements that may encode a wide range of resistance genes and give resistant phenotypes to several types of antibiotics. To date, the epidemiology, gene content and fitness impact of ICEs are poorly characterized. ICEs transfer between bacteria via the mechanism of conjugation. Conjugation is a major cause of antibiotic resistance dissemination and identification of specific conjugation inhibitors (COINs) is therefore of utmost importance. In this project, we will determine the role of ICEs in the spread of antibiotic resistance in H. influenzae strains and determine whether COINs can inhibit dissemination of such ICEs. We will screen Scandinavian invasive H. influenzae strains for the presence of ICEs, characterize selected strains, and use a subset of these to perform state-of-the-art in vitro experiments in Norway and The United Kingdom. If one or more COINs efficiently inhibit transfer of ICEs, we will design and apply for approval of a future animal study. Our project aims to identify specific COINs that can inhibit dissemination of antibiotic resistance in vivo, ensuring safe empiric patient therapy and preserving effective antibiotics for future generations.
