Why put up with immunity when there is resistance: An excursion into the population and evolutionary dynamics of restriction-modification and CRISPR-Cas

• Type of Material: Article
• Authors: James Gurney, Georgia Institute of Technology; Marcos Pleška, The Rockefeller University; Bruce Levin, Emory University
• Language: English
• Date: 2019-05-13
• Publisher: Royal Society, The
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1098/rstb.2018.0096
• Title of Journal or Parent Work: Philosophical Transactions B: Biological Sciences
• ISSN: 0962-8436
• Volume: 374
• Issue: 1772
• Start Page: 20180096
• End Page: 20180096
• Grant/Funding Information: This endeavour was supported by a grant from the Simons Foundation (396001), J.G., and a grant from the US National Institutes of Health, R01-GM091875, B.R.L.
• Keywords: CRISPR-Cas; immunity; restriction–modification; bacteriophage; resistance
• Research Categories: Health Sciences, Immunology

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'.