Epidemiological and evolutionary consequences of different types of CRISPR-Cas systems

Bacteria have adaptive immunity against viruses (phages) in the form of CRISPR-Cas immune systems. Currently, 6 types of CRISPR-Cas systems are known and the molecular study of three of these has revealed important molecular differences. It is unknown if and how these molecular differences change the outcome of phage infection and the evolutionary pressure the CRISPR-Cas systems faces. To determine the importance of these molecular differences, we model a phage outbreak entering a population defending exclusively with a type I/II or a type III CRISPR-Cas system. We show that for type III CRISPR-Cas systems, rapid phage extinction is driven by the probability to acquire at least one resistance spacer. However, for type I/II CRISPR-Cas systems, rapid phage extinction is characterized by an a threshold-like behaviour: any acquisition probability below this threshold leads to phage survival whereas any acquisition probability above it, results in phage extinction. We also show that in the absence of autoimmunity, high acquisition rates evolve. However, when CRISPR-Cas systems are prone to autoimmunity, intermediate levels of acquisition are optimal during a phage outbreak. As we predict an optimal probability of spacer acquisition 2 factors of magnitude above the one that has been measured, we discuss the origin of such a discrepancy. Finally, we show that in a biologically relevant parameter range, a type III CRISPR-Cas system can outcompete a type I/II CRISPR-Cas system with a slightly higher probability of acquisition. Author summaryCRISPR-Cas systems are adaptive immune systems that use a complex 3-step molecular mechanism to defend prokaryotes against phages. Viral infections of populations defending themselves with CRISPR-Cas can result in rapid phage extinction or in medium-term phage maintenance. To investigate what controls the fate of the phage population, we use mathematical modeling of type I/II and type III CRISPR-Cas systems, and show that two parameters control the epidemiological short-term outcome: the type of CRISPR-Cas systems and CRISPR-Cas probability of resistance acquisition. Furthermore, the latter impacts host fitness. From this, we derive that 1) for both types, CRISPR-Cas acquisition probability is a key predictor of the efficiency and of the cost of a CRISPR-Cas system, 2) during an outbreak, there is an optimal probability of resistance acquisition balancing the cost of autoimmunity and immune efficiency and 3) type I/II CRISPR-Cas systems are likely to evolve higher acquisition probability than type III.

Automated summary

Bacteria have adaptive immunity against phages through CRISPR-Cas immune systems. Different types of CRISPR-Cas systems have molecular differences that affect the outcome of phage infection and the evolutionary pressure. The probability of acquiring resistance spacer plays a crucial role in phage extinction. Type III CRISPR-Cas systems exhibit a rapid phage extinction driven by spacer acquisition, while type I/II systems have a threshold-like behavior. Autoimmunity affects the acquisition rates. In a biologically relevant parameter range, type III systems can outcompete type I/II systems with a slightly higher acquisition probability.