How do parasitic worms act as islands of antibiotic resistance?

More than 2 billion people worldwide are infected with parasitic worms (helminths). These infections cause significant disease as well as widespread changes in the host immune system and general physiology. This includes increased susceptibility to some bacterial pathogens, such as salmonella [1]. This is often attributed to the ability of the worm to modify (and turn-off) host immune responses, including those directed against the bacteria. Salmonella serovars can infect both humans and livestock, and specific serovars are able to cause serious invasive disease.

In addition to modifying host immune responses, it has been known for more than 30 years that parasitic worms such as schistosomes can provide a convenient platform for bacterial colonization and growth [2]. Direct bacteria-helminth interactions offer the bacteria a privileged position, safe from the host immune system. Importantly, worm-associated bacteria display anti-microbial resistance (AMR). We now have the experimental tools to gain a molecular understanding of the mechanisms of bacterial attachment to the worm, and biological consequences for both the bacteria and the worm.

In this project, the student will focus on characterising the bacterial and worm molecules responsible for this in vivo interaction, through the use of microbiology, molecular biology, parasitology and ‘omic approaches (e.g. glycomics [3], next-gen sequencing). Experiments will be performed using an in vivo murine model of schistosomiasis and through in vitro studies, with parasite-bacteria interactions visualised using cutting-edge imaging techniques. We will investigate how worm-associated bacteria escape antibiotic selective pressure. The schistosome surface is a metabolically active and dynamic structure, and so it is highly unlikely worms simply act as inert supports for bacterial growth. Instead, we will explore how the worm responds to its bacterial passenger – by providing a nourishing environment and safe haven from the host immune response, or by fighting back and limiting bacterial growth through as yet unexplored mechanisms.

The project will provide training in both host-pathogen and pathogen-pathogen interactions, with direct supervision from helminth and microbiology experts, and will make extensive use of a wide-range of imaging and molecular strategies to investigate this cross-kingdom communication. This project also benefits from international collaborations with glycobiology experts.

This project will be suitable for a graduate in biology, biomedical sciences, biochemistry, or related subjects, with a strong interest in and background knowledge of infection biology.