Keeping crispr in check: diverse mechanisms of phage-encoded anti-crisprs.

Despoina Trasanidou,Franklin L Nobrega,Ana Sousa Gerós,Anna Cornelia Nieuwenweg,Prarthana Mohanraju,Raymond H J Staals

doi:10.1093/femsle/fnz098

Despoina Trasanidou, Franklin L Nobrega + Show 4 more

Open Access

https://doi.org/10.1093/femsle/fnz098

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Abstract

ABSTRACTCRISPR-Cas represents the only adaptive immune system of prokaryotes known to date. These immune systems are widespread among bacteria and archaea, and provide protection against invasion of mobile genetic elements, such as bacteriophages and plasmids. As a result of the arms-race between phages and their prokaryotic hosts, phages have evolved inhibitors known as anti-CRISPR (Acr) proteins to evade CRISPR immunity. In the recent years, several Acr proteins have been described in both temperate and virulent phages targeting diverse CRISPR-Cas systems. Here, we describe the strategies of Acr discovery and the multiple molecular mechanisms by which these proteins operate to inhibit CRISPR immunity. We discuss the biological relevance of Acr proteins and speculate on the implications of their activity for the development of improved CRISPR-based research and biotechnological tools.

Highlights

Viruses are ubiquitous entities co-existing with cellular life forms, present in almost all explored environments (Koonin and Dolja 2013)
These immune systems are widespread among bacteria and archaea, and provide protection against invasion of mobile genetic elements, such as bacteriophages and plasmids
As a result of the arms-race between phages and their prokaryotic hosts, phages have evolved inhibitors known as anti-Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) (Acr) proteins to evade CRISPR immunity

Summary

INTRODUCTION

Viruses are ubiquitous entities co-existing with cellular life forms, present in almost all explored environments (Koonin and Dolja 2013). The cas genes encode for the Cas proteins, which are necessary for the generation of new spacers or are involved in the targeting of the MGE, as explained below These two elements of CRISPR-Cas systems mediate sequence-specific immunity against invasive MGEs (Brouns et al 2008; Marraffini and Sontheimer 2008; Hale et al 2009; Garneau et al 2010). Acr proteins have distinct sequences (Tables 1 and 2), structures (Maxwell et al 2016; Wang et al 2016a; Harrington et al 2017) and mechanisms (Bondy-Denomy et al 2015) and they provide phages with a direct and specific means to inhibit targeting by the CRISPR-Cas system. The emergence of widespread, specialized and highly diverse phage-encoded proteins that thwart CRISPR-Cas immunity, suggests that Acr proteins play an important role in phage

98 Sulfolobus islandicus Functional assays

Method of discovery