INVADER · Caught or Spared: Exploring the Cellular Rules of Bacterial Predation

Antimicrobial resistance is eroding the effectiveness of antibiotics, driving the search for novel antibacterial strategies. Predatory bacteria such as Bdellovibrio bacteriovorus (Bb) are promising because they invade the cell envelope of diderm bacteria – including pathogens – and consume their contents to proliferate. Despite their remarkable killing capacities, the mechanisms underlying prey recognition, invasion, and digestion remain unclear, as do the cellular features that render some species susceptible while others resist.The INVADER project takes a prey-centred, multi-scale approach to define predation determinants. WP1 will use a genetically tractable prey model, Escherichia coli, to monitor in detail how each cellular compartment is remodelled during the Bb attack cycle, using fluorescent reporters, microfluidics, and high-resolution live imaging. WP2 will systematically assess Bb predation across forty ecologically and clinically diverse diderm species, combining standardised killing assays and single-cell microscopy to produce a quantitative, comparative map of predation susceptibility. WP3 will identify genetic determinants underlying predation using high-throughput Tn-seq and CRISPRi screens in E. coli strains with contrasting predation susceptibility phenotypes, and link them to phenotypes via single-cell imaging. Finally, phylogenetic analysis across the WP2 strain panel will reveal how the distribution of key predation determinants from WP3 correlates with susceptibility in diverse bacteria, enabling prediction of Bb predation efficiencies in untested species.This integrated, interdisciplinary strategy – grounded in open science practices and strengthened by international collaborations – will deliver mechanistic and predictive insights into bacterial predation, bridging a long-standing knowledge gap, uncover conserved vulnerabilities in bacterial envelopes, and pave the way for predator-inspired biocontrol and microbiome-engineering applications