Microbial treasure trove : Unravelling the potential of class 2 CRISPR–Cas systems

Abstract

General introduction and thesis outline 1Prokaryotes versus viruses PRoKaRyotes veRsus viRusesL ife on earth is comprised of three domains; the Bacteria, the Archaea, and the Eukarya. Survival of all forms of life is continuously confronted by their constantly changing surroundings. Prokaryotes (bacteria and archaea) dominate many natural habitats, including some highly competitive and harsh environments. They thrive in such environments despite facing a constant threat of invasions by selfish Mobile Genetic Elements (MGEs) such as transposons, plasmids and viruses. Bacteriophages (phages), are the viruses of bacteria that have been estimated to be the most abundant biological entities on the planet with population numbers in the order of 10³¹ (1, 2). Phages are divided into two groups, virulent and temperate. Virulent phages follow a strictly productive lytic life cycle for propagation which ultimately kills the host for the release of new viral particles, each of which can engage in another round of infection. Temperate phages have the choice to switch between productive and dormant states. They either multiply in their host cells leading to cell lysis similar to virulent phages or integrate their phage genome into the bacterial chromosome to become a 'dormant' prophage. Prophages are propagated passively by the replication machinery of the bacterial cell (3). Microscopic phage-bacteria interactions have quite a profound effect on the macroscopic scale as they strongly influence global biogeochemical cycles (4), global climate (5), incidence of human diseases ( 6), as well as patterns of microbial genome diversity (7).The Red Queen hypothesis (Box 1) posits that antagonistic biotic interactions, such as those displayed by hosts and parasites, generates a selective pressure on host organisms to continuously evolve systems that neutralize infections leading to adaptations of the host and counteradaptations on the parasite's end (8). The continuous arms race of developing infection and resistance strategies results in a rapid co-evolution of the parasite's offence systems and host defence systems. Such an evolutionary trend is extremely prominent in phage-microbe interactions. This is mainly due to the rapid evolution and turnover of phage particles (4) leading to acute selective pressure on microbial communities to evade infection by developing immunity.