CRISPR targeting of the V. cholerae small chromosome can overcome PLE, but our results suggest a model in which there is a limit to the distance over which processive Cas2-3 degradation can occur to reach the PLE prior to excision (figure 7), an action which occurs within 5 min of ICP1 infection that is directed by an early expressed ICP1 protein [20]. The gene discussed is ATP8B1; the disease is infection.