Variability in the durability of CRISPR-Cas immunity

Abstract

The durability of host resistance is challenged by the ability of pathogens to escape the defence of their hosts. Understanding the variability in the durability of host resistance is of paramount importance for designing more effective control strategies against infectious diseases. Here, we study the durability of various clustered regularly interspaced short palindromic repeats-Cas (CRISPR-Cas) alleles of the bacteria Streptococcus thermophilus against lytic phages. We found substantial variability in durability among different resistant bacteria. Since the escape of the phage is driven by a mutation in the phage sequence targeted by CRISPR-Cas, we explored the fitness costs associated with these escape mutations. We found that, on average, escape mutations decrease the fitness of the phage. Yet, the magnitude of this fitness cost does not predict the durability of CRISPR-Cas immunity. We contend that this variability in the durability of resistance may be because of variations in phage mutation rate or in the proportion of lethal mutations across the phage genome. These results have important implications on the coevolutionary dynamics between bacteria and phages and for the optimal deployment of resistance strategies against pathogens and pests. Understanding the durability of CRISPR-Cas immunity may also help develop more effective gene-drive strategies based on CRISPR-Cas9 technology. This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.

Non-retroviral Endogenous Viral Element Limits Cognate Virus Replication in Aedes aegypti Ovaries

“…Therefore, viruses could escape EVE-mediated immunity by acquiring mutations, resulting in a possible coevolutionary arms race. Predicting the tempo and mode of such coevolutionary dynamics is difficult, even when the fitness cost of individual mutations is known [53]. Interestingly, in our study, the NS2 region of the CFAV EVE was most tightly involved in the interaction with the virus.…”

The effect of phage genetic diversity on bacterial resistance evolution

“…Although CRISPR-Cas systems are found in a diverse range of habitats, there is a highly uneven distribution across different environments. Metagenomic sequence analyses have shown that the frequency of the evolution and maintenance of CRISPR-Cas systems in bacterial and archaeal communities may be linked to environmental factors as higher frequencies of CRISPR-Cas are often found in extreme environments [18]. This suggests that there are environmental attributes that constrain the fitness advantages (or ecological success) of this form of phage defence.…”

“…Processed CRISPR transcripts guide Cas proteins to detect and destroy reinfecting phage that carry the cognate target sequence [12,13]. Phage can in turn overcome CRISPR-based immunity by acquiring a point mutation in the target sequence on their genome [14], although the emergence and spread of such phage "escape" mutants is constrained by both the diversity of CRISPR immunity alleles in the bacterial population and the fitness costs associated with the phage mutations [15][16][17][18].…”

Long-run bacteria-phage coexistence dynamics under natural habitat conditions in an environmental biotechnology system

“…In contrast, in our study we observed directional changes, yet accumulation of mutations in the PAM and protospacer regions was not favored ( Fig 4 ). This is not surprising, given that phages that escape bacterial immunity by mutating their target protospacers within one host will not be successful against coexisting bacterial populations that possess different spacers [64]. Yet, as long as no individual bacterial population achieves a much higher density than their competitors, phages would still find excess of susceptible hosts, reducing the selection pressure to mutate their targeted protospacers or PAM regions.…”