The arms race between bacteria and phages

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 (Ofir & Sorek, Cell 2018). We study this arms race in order to understand how the extensive co-evolution of both phage and host shapes the huge diversity of the microbial world (Bernheim et al, Nature Reviews Microbiology 2020).

As part of our reserach, we study the CRISPR-Cas system, an adaptive immunity system widespread in prokaryotes that defends against phage (Levy et al, Nature 2015). We also use genomics and molecular evolution techniques to search for novel anti-phage defense systems in microbial genomes. Specifically, we discovered BREX, a novel 6-gene anti-phage defense system found in 10% of all bacteria and archaea (Goldfarb et al, EMBO J 2015), DISARM, a 5-gene new defense system with broad anti-phage activities (Ofir et al, Nature Microbiology 2018), and many additional defense systems that protect bacteria against phages (Doron et al, Science 2018). We found that some bacterial defense systems are the ancient ancestors of important components of the human innate immune system (Doron et al, Science 2018; Cohen et al, Nature 2019; Morehouse et al, Nature 2020; Bernheim et al, Nature 2021).

Another discovery from our lab shows that some phages use small-molecule communication to coordinate their infection dynamics (Erez et al, Nature 2017). We found such communication systems in hundreds of different phages (Stokar-Avihail et al, Cell Host & Microbe 2019).

In additional studies, we found how bacterial genomes evolve in response to phage attacks (Avrani et al, Nature 2011), and followed the transcriptional program of phages when infecting their hosts, identifying new modes of regulation (Doron et al, ISME J 2016). The arms race between phages and bacteria residing in the human gut is also studied in our lab. We identified almost 1000 phages the infect bacteria that inhabit the human gut, and showed that these phages are shared among geographically distant human populations, possibly affecting human health (Stern, Mick et al, Genome Research 2012).

BREX

(A) The BREX anti-phage defense system, discovered at the Sorek lab (B) Operon organization of BREX (C-E) Infection experiments with two phages. Shown are culture dynamics of phage-infected wild type (black) versus a system-containing (red) strain of B. subtilis. (F) Plaque assay with serial phage dilution. Complete protection is observed even at the highest phage concentrations.

(Figure adapted from Goldfarb et al., EMBO J 2015))