Arbitrium communication controls phage lysogeny through non-lethal modulation of a host toxin-antitoxin defence system.

Temperate Bacillus phages often utilize arbitrium communication to control lysis/lysogeny decisions, but the mechanisms by which this control is exerted remains largely unknown. Here we find that the arbitrium system of Bacillus subtilis phage ϕ3T modulates the host-encoded MazEF toxin-antitoxin system to this aim. Upon infection, the MazF ribonuclease is activated by three phage genes. At low arbitrium signal concentrations, MazF is inactivated by two phage-encoded MazE homologues: the arbitrium-controlled AimX and the later-expressed YosL proteins. At high signal, MazF remains active, promoting lysogeny without harming the bacterial host. MazF cleavage sites are enriched on transcripts of phage lytic genes but absent from the phage repressor in ϕ3T and other Spß-like phages. Combined with low activation levels of MazF during infections, this pattern explains the phage-specific effect. Our results show how a bacterial toxin-antitoxin system has been co-opted by a phage to control lysis/lysogeny decisions without compromising host viability.

Abortive infection antiphage defense systems: separating mechanism and phenotype.

Bacteria have evolved a wide array of mechanisms that allow them to eliminate phage infection. 'Abortive infection' (abi) systems are an expanding category of such mechanisms, defined as those which induce programmed cell death (or dormancy) upon infection, and thus halt phage propagation within a bacterial population. This definition entails two requirements - a phenotypic observation (cell death upon infection), and a mechanistic determination of its sources (system-induced death). The phenotypic and mechanistic aspects of abi are often implicitly assumed to be tightly linked, and studies regularly tend to establish one and deduce the other. However, recent evidence points to a complicated relationship between the mechanism of defense and the phenotype observed upon infection. We argue that rather than viewing the abi phenotype as an inherent quality of a set of defense systems, it should be more appropriately thought of as an attribute of interactions between specific phages and bacteria under given conditions. Consequently, we also point to potential pitfalls in the prevailing methods for ascertaining the abi phenotype. Overall, we propose an alternative framework for parsing interactions between attacking phages and defending bacteria.

Dormant phages communicate via arbitrium to control exit from lysogeny.

Temperate bacterial viruses (phages) can transition between lysis-replicating and killing the host-and lysogeny, that is, existing as dormant prophages while keeping the host viable. Recent research showed that on invading a naïve cell, some phages communicate using a peptide signal, termed arbitrium, to control the decision of entering lysogeny. Whether communication can also serve to regulate exit from lysogeny (known as phage induction) is unclear. Here we show that arbitrium-coding prophages continue to communicate from the lysogenic state by secreting and sensing the arbitrium signal. Signalling represses DNA damage-dependent phage induction, enabling prophages to reduce the induction rate when surrounded by other lysogens. We show that in certain phages, DNA damage and communication converge to regulate the expression of the arbitrium-responsive gene aimX, while in others integration of DNA damage and communication occurs downstream of aimX expression. Additionally, signalling by prophages tilts the decision of nearby infecting phages towards lysogeny. Altogether, we find that phages use small-molecule communication throughout their entire life cycle to sense the abundance of lysogens in the population, thus avoiding lysis when they are likely to encounter established lysogens rather than permissive uninfected hosts.

Short-range quorum sensing controls horizontal gene transfer at micron scale in bacterial communities.

In bacterial communities, cells often communicate by the release and detection of small diffusible molecules, a process termed quorum-sensing. Signal molecules are thought to broadly diffuse in space; however, they often regulate traits such as conjugative transfer that strictly depend on the local community composition. This raises the question how nearby cells within the community can be detected. Here, we compare the range of communication of different quorum-sensing systems. While some systems support long-range communication, we show that others support a form of highly localized communication. In these systems, signal molecules propagate no more than a few microns away from signaling cells, due to the irreversible uptake of the signal molecules from the environment. This enables cells to accurately detect micron scale changes in the community composition. Several mobile genetic elements, including conjugative elements and phages, employ short-range communication to assess the fraction of susceptible host cells in their vicinity and adaptively trigger horizontal gene transfer in response. Our results underscore the complex spatial biology of bacteria, which can communicate and interact at widely different spatial scales.

A Bacterial Tower of Babel: Quorum-Sensing Signaling Diversity and Its Evolution.

Quorum sensing is a process in which bacteria secrete and sense a diffusible molecule, thereby enabling bacterial groups to coordinate their behavior in a density-dependent manner. Quorum sensing has evolved multiple times independently, utilizing different molecular pathways and signaling molecules. A common theme among many quorum-sensing families is their wide range of signaling diversity-different variants within a family code for different signal molecules with a cognate receptor specific to each variant. This pattern of vast allelic polymorphism raises several questions-How do different signaling variants interact with one another? How is this diversity maintained? And how did it come to exist in the first place? Here we argue that social interactions between signaling variants can explain the emergence and persistence of signaling diversity throughout evolution. Finally, we extend the discussion to include cases where multiple diverse systems work in concert in a single bacterium.