Abstract
SummaryBacillus phages use a communication system, termed “arbitrium,” to coordinate lysis-lysogeny decisions. Arbitrium communication is mediated by the production and secretion of a hexapeptide (AimP) during lytic cycle. Once internalized, AimP reduces the expression of the negative regulator of lysogeny, AimX, by binding to the transcription factor, AimR, promoting lysogeny. We have elucidated the crystal structures of AimR from the Bacillus subtilis SPbeta phage in its apo form, bound to its DNA operator and in complex with AimP. AimR presents intrinsic plasticity, sharing structural features with the RRNPP quorum-sensing family. Remarkably, AimR binds to an unusual operator with a long spacer that interacts nonspecifically with the receptor TPR domain, while the HTH domain canonically recognizes two inverted repeats. AimP stabilizes a compact conformation of AimR that approximates the DNA-recognition helices, preventing AimR binding to the aimX promoter region. Our results establish the molecular basis of the arbitrium communication system.
Highlights
Temperate bacteriophages can switch between their lytic and lysogenic life cycles
The phages produce a peptide (AimP) as a signal to communicate during phage infection (Erez et al, 2017). This system, termed ‘‘arbitrium,’’ seems to be used by a large group of SPbeta Bacillus phages and is composed of three genes: aimP, which encodes the arbitrium peptide, aimR, encoding a transcription factor that interacts with AimP, and aimX, which produces a small non-coding RNA
AimR Displays a High Conformational Plasticity To establish the molecular basis of this novel mechanism of phage communication we produced crystals of AimR in its apo form that diffracted to 2.7Aand belong to space group P21 with eight monomers in the asymmetric unit (Table 1)
Summary
Temperate bacteriophages can switch between their lytic and lysogenic life cycles. While this lytic-lysogeny selection is one of the key decisions in the biology of temperate phages, our understanding of the molecular mechanisms underpinning the decision-making process is still very limited, concentrating mainly on the model Escherichia coli l phage (Golding, 2016). A novel decision-making system involved in phage induction/repression has been recently reported using the Bacillus subtilis phi3T phage as a model In this elegant system, the phages produce a peptide (AimP) as a signal to communicate during phage infection (Erez et al, 2017). AimP will accumulate in the medium as a consequence of the excessive phage replication, until its concentration reaches the threshold level required to bind to its cognate AimR receptor (Erez et al, 2017) This important interaction promotes the switch to the lysogenic cycle and impairs the killing of the entire bacterial population by the phage. It has been hypothesized that AimR receptors from different phages are regulated by their cognate arbitrium peptide, suggesting that phages only communicate with their progeny (Erez et al, 2017)
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