PhD project

Supervisor: Emma Slack

Antibiotic-resistant Enterococcus infections are a growing problem in hospitalized patients worldwide, with high mortality rates(1). Vaccine- and immunotherapy-based decolonization approaches to control Enterococci could offer an alternative to antibiotics, but require major advancements in our understanding of immunogenic structures on the surface of pathogenic Enterococci. While we have extensive knowledge on immune recognition of model Gammaproteobacterial species such as E. coli and Salmonella (2, 3), the Bacillota (of which Enterococcus is a member) diverged from the Pseudomonadota prior to the evolution of Eukaryotes, such that extrapolation between these bacterial phyla is dangerous! Notably, the mammalian immune system is around 1000-fold less sensitive to pathogen-associated molecular patterns such as lipopeptides from gram-positive bacteria than they are to lipidA from gram-negative bacteria, hinting at major differences in immunological relationships with these species(4).

In this project we will use vaccination and single-cell sequencing to generate monoclonal antibodies specific for surface structures of Enterococcus faecium and Enterococcus faecalis species. We will determine the specificity and binding characteristics of these antibodies, and will explore the ability of antibodies with different bacterial binding characteristics to driving killing and aggregation of clinical isolates of Enterococcus. This information will guide the design of vaccines aimed at suppressing Enterococcus overgrowth in the gut and preventing bloodstream infections

The project will span bacterial genomics, glycobiology, recombinant antibody technologies, in vivo infection biology and vaccine design/mucosal immunology.

Keywords:

Immunology, Glycobiology, Microbiology, Molecular Biology

Publications:

1. C.A. Arias, B. E. Murray, The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 10, 266-278 (2012).
2. Diard et al., A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants. Nature Microbiology 6, 830-841 (2021).
3. Lentsch et al., Vaccine-enhanced competition permits rational bacterial strain replacement in the gut. Science 388, 74-81 (2025).
4. Li, M. Wu, Pattern recognition receptors in health and diseases. Signal Transduction and Targeted Therapy 6, 291 (2021).