Highlights
- •Activation of phage VP882 results in complex transcriptional changes in V. cholerae
- •The Hfq RNA chaperone supports interactions of host- and phage-encoded transcripts
- •The phage-encoded VpdS sRNA facilitates phage replication
- •Host-encoded sRNAs inhibit phage replication through base-pairing interactions
Summary
Many, if not all, bacteria use quorum sensing (QS) to control collective behaviors, and more recently, QS has also been discovered in bacteriophages (phages). Phages can produce communication molecules of their own, or “listen in” on the host’s communication processes, to switch between lytic and lysogenic modes of infection. Here, we study the interaction of Vibrio cholerae with the lysogenic phage VP882, which is activated by the QS molecule DPO. We discover that induction of VP882 results in the binding of phage transcripts to the major RNA chaperone Hfq, which in turn outcompetes and downregulates host-encoded small RNAs (sRNAs). VP882 itself also encodes Hfq-binding sRNAs, and we demonstrate that one of these sRNAs, named VpdS, promotes phage replication by regulating host and phage mRNA levels. We further show that host-encoded sRNAs can antagonize phage replication by downregulating phage mRNA expression and thus might be part of the host’s phage defense arsenal.
Introduction
Bacteriophages, or short phages, are viruses that prey on bacteria and are considered the most abundant biological entities in the biosphere.1 The interaction of phages with their hosts is highly diverse and likely one of the major drivers of bacterial evolution.2 More recently, research on host-phage interactions has uncovered a plethora of bacterial defense strategies that frequently constitute ancient homologs of eukaryotic immune systems.3,4 Likewise, phages have developed sophisticated counter-defense strategies that target bacterial immunity, revealing an ongoing arms race between phages and their hosts.5
Viruses and phages have long been considered solitary entities. However, this view has now been challenged by the discovery of various phage-encoded quorum sensing (QS)-like communication systems.6 For example, phi3T, a lysogenic phage infecting Bacillus subtilis, employs a peptide-mediated communication strategy (called the arbitrium system) to measure phage concentration in the vicinal environment and to coordinate the switch between lytic and lysogenic lifestyles.7 Similarly, the lysogenic vibriophage VP882 harnesses a phage-encoded transcription factor that is homologous to the VqmA QS receptor protein of its host.8,9 Both proteins respond to the autoinducer molecule, 3,5-dimethylpyrazin-2-ol (DPO); however, only the phage-encoded VqmA protein activates the lytic program in VP882. Here, phage VqmA induces the production of a small protein, called Qtip, that sequesters the CI repressor protein of VP882 and thereby activates the phage lysis program8 (Figure 1A). Of note, analogous communication systems have now been discovered on hundreds of phage genomes, indicating that QS sensing phages are prevalent in nature…
