Mechanisms of bacterial killing by degradation of the cell envelope

Bart Hoogenboom (primary)
London Centre for Nanotechnology
University College London
Jeremy Brown (secondary)
Medicine
UCL

Abstract

With this project, we aim to determine how membrane-targetting antimicrobials such as complement proteins and antimicrobial peptides kill bacteria by degradation of the bacterial cell envelope. Our approach will be based on recent advances in atomic force microscopy in Hoogenboom’s lab, which now enable us to monitor – at nanometre resolution and in real time – surface structure and mechanics of bacterial surfaces under attack by anti-bacterial proteins, while simultaneously verifying bacterial killing using fluorescence-based live-dead staining. By understanding how our immune system kills bacteria, we will provide guidance for the development of new therapies to overcome antimicrobial resistance.


References

E. De Santis et al., Nature Communications 8, 2263 (2017).
D. A. Heesterbeek et al., EMBO Journal, e99852 (2019).
C. Leung et al., Nature Nanotechnology 12, 467–473 (2017).
E. Parsons et al., Nature Communications 10, 2066 (2018).
E. Ramos-Sevillano et al. PLOS Pathogens, 12, e1005500 (2016).
J. S. Brown et al. PNAS USA, 99, 16969-16974 (2002).
J. Yuste et al. J Immunology, 175, 1813-1819 (2005).


BBSRC Area
Molecules, cells and industrial biotechnologyPlants, microbes, food and sustainability
Area of Biology
ImmunologyMicrobiology
Techniques & Approaches
BiophysicsMicroscopy / Electrophysiology