PHAGECOM · Complex parasite communities as drivers of bacterial immunity

Complex parasite communities as drivers of bacterial immunity

CRISPR-Cas is one of several distinct bacterial defence mechanisms that provide immunity against viruses (phages) and other mobile genetic elements (MGEs), including plasmids. While the biochemistry of CRISPR-Cas is now well understood, its importance in host-pathogen co-evolution is unclear. Although CRISPR-Cas is clearly important for evolving resistance against MGE in nature, my previous work has shown that under laboratory conditions other resistance mechanisms are more important. This raises the question: under what ecological conditions is CRISPR-Cas-mediated resistance important for evolving MGE resistance? This research project studied how MGE community complexity affects CRISPR-Cas evolution, revealing conditions that increase or decrease CRISPR-Cas efficacy (e.g. the use of multiple phage species and the role of anti-CRISPR genes encoded on phage genomes). This knowledge has important consequences for society as it can be directly implemented in phage therapy to combat pathogenic bacteria and in the dairy industry to protect bacterial starter cultures. In addition, CRISPR-Cas is now widely used as a tool in genome editing, and this has massive potential for the treatment of genetic diseases and crop improvement. The overall aim of this project was to study the role of CRISPR-Cas in the face of a complex MGE community consisting of phages and plasmids. I had the following research objectives: i. Study the evolution and efficacy of CRISPR-Cas-mediated immunity. ii. Study the fitness consequences of CRISPR-Cas over surface modification by competing bacteria in the presence or absence of MGE. iii. Analyse molecular evolution of bacteria and MGE throughout co-evolution experiments. This will be done by deep sequencing of bacterial and phage genomes isolated at different time points. iv. Analyse the co-evolutionary dynamics associated with CRISPR-Cas. Main conclusions: 1. PA14 CRISPR-Cas systems do not co-evolve with phages, but instead drive phages extinct due to the generation of population-level CRISPR diversity. 2. Metapopulation dynamics (i.e. immigration of sensitive bacteria) leads to higher levels of phage persistence, but not co-evolution with CRISPR-Cas. 3. Population-level CRISPR diversity limits the ability for phage to locally adapt to their hosts. 4. Phages carrying anti-CRISPRs can cause epidemics on CRISPR-resistant bacteria when phage densities are high enough.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз