The phage-host arms race: shaping the evolution of microbes

Abstract

Bacteria, the most abundant organisms on the planet, are outnumbered by a factor of 10 to 1 by phages that infect them. Faced with the rapid evolution and turnover of phage particles, bacteria have evolved various mechanisms to evade phage infection and killing, leading to an evolutionary arms race. The extensive co-evolution of both phage and host has resulted in considerable diversity on the part of both bacterial and phage defensive and offensive strategies. Here, we discuss the unique and common features of phage resistance mechanisms and their role in global biodiversity. The commonalities between defense mechanisms suggest avenues for the discovery of novel forms of these mechanisms based on their evolutionary traits.

Figure 1. The restriction-modification defense system

A: A general illustration of function, exemplified by type II R–M enzymes. B: Examples of strategies employed by phage to evade restriction. (1) Incorporation of unusual bases protects from restriction [15]; (2) Masking of the restriction sites by phage proteins[112]; (3) Stimulation of MTase activity causes the phage DNA to be protected; (4) Neutralization of REase by phage proteins that mimic DNA [113].

Figure 2. The CRISPR/Cas system

A: Mechanism of action: transcription from the repeat-spacer CRISPR locus generates a long non-coding RNA, with repeats that may sometimes assume a secondary structure. Cleavage of the repeat sequences by the Cas proteins generates crRNAs that target the phage DNA or RNA, and interfere with phage infection. B: Phages can evade CRISPR interference by mutation or recombination of the targeted proto-spacer sequence. Another putative evasion mechanism is phosphorylation of the Cas proteins. This remains, however, to be verified.

Figure 3. The abortive infection system

A: Illustration of the mechanism of the E. coli K-12 abortive infection Lit system. When the T4 phage peptide Gol is synthesized, it binds and activates the bacterial (prophage-encoded) Lit protein, which then cleaves the elongation factor EF-Tu. This leads to the arrest of protein synthesis and to bacterial cell death, with the phage trapped inside. B: A mutation at the Gol polypeptide reduces the activation of Lit, and rescues the phage.