Decoding inter-species PICI transfer to understand bacterial evolution and design next-generation antibacterial therapies. (360G-Wellcome-321818_Z_24_Z)

Antibiotic resistance intensifies the need to understand mechanisms driving bacterial evolution. Our research uncovered a novel mechanism by which certain phage-inducible chromosomal islands (PICIs), known as "capsid-forming PICIs" (cf-PICIs), utilise phage tails from unrelated bacteria to form chimeric particles that enable inter-species transfer. Since cf-PICIs encode virulence and antibiotic resistance genes, this process fuels their dissemination in nature. Supported by genomic and structural analyses, this discovery shows cf- PICIs can produce a new type of biological entity: small capsids containing cf-PICI DNA. These tail-less, non-infective particles, once released into bacterial communities, acquire phage tails from various bacterial species. This process expands their bacterial host range via chimeric, infective particles. This project will decode this transfer mechanism to understand how cf-PICIs interact with diverse phage tails, enabling broader host targeting. Additionally, since phages use DNA packaging and particle formation strategies similar to cf-PICIs, we will investigate whether phages employ comparable mechanisms to expand their host range. We propose to harness this inter- species transfer capability to establish the basis for developing tailored cf- PICI and phage-based therapies to combat antibiotic resistance. This research could pioneer novel therapeutic approaches against bacterial infections while providing significant insights into bacterial evolution and managing microbial ecosystems.