Abstract
Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction–modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions under which selection mediated by lytic phage will favour such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the number of steps in the coevolutionary arms race between the bacteria-acquiring spacers and the phage-generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Highlights
The two most widely used tools for manipulating and editing DNA—restriction and Cas9 endonucleases—both originate from studies of mechanisms that provide bacteria with immunity to infections with lytic bacteriophage: restriction modification (RM) originally identified in Escherichia coli [1,2] and CRISPR-Cas found in Streptococcus thermophilus [3], respectively.RM systems allow bacteria to distinguish self DNA from non-self DNA by methylating specific DNA sequences called restriction sites
The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the number of steps in the coevolutionary arms race between the bacteria-acquiring spacers and the phage-generating CRISPR-escape mutants
Why would bacteria evolve and maintain dedicated molecular mechanisms like RM and CRISPR-Cas to prevent phage infections if mutations leading to envelope resistance can be readily generated? Here, we address this question with the aid of mathematical and computer simulation models of the population and evolutionary dynamics of bacteria confronted with lytic phage
Summary
The two most widely used tools for manipulating and editing DNA—restriction and Cas endonucleases—both originate from studies of mechanisms that provide bacteria with immunity to infections with lytic bacteriophage ( phage): restriction modification (RM) originally identified in Escherichia coli [1,2] and CRISPR-Cas found in Streptococcus thermophilus [3], respectively. By modifying tail fibres or other structures used to adsorb to the bacteria, the phage can generate host-range mutants that overcome resistance by adsorbing to different receptors [23] How common this is and for how long such an arms race 2 can continue is, currently unclear. (iii) If mutations leading to envelope resistance can be generated, the contribution of CRISPR-Cas– mediated immunity to protecting the bacteria from phage depends on a number of factors, most important of which is the number of steps in the arms race between bacteria acquiring new spacers and the phage generating escape mutants The phage escape restriction and are modified, envelope resistant mutants are likely to ascend. (iii) If mutations leading to envelope resistance can be generated, the contribution of CRISPR-Cas– mediated immunity to protecting the bacteria from phage depends on a number of factors, most important of which is the number of steps in the arms race between bacteria acquiring new spacers and the phage generating escape mutants
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