Temperate viruses can become dormant in their host cells, a process called lysogeny. In every infection, such viruses need to decide between the lytic and the lysogenic cycles, i.e., whether to replicate and lyse their host or to lysogenize and keep the host viable. Here we show that viruses (phages) of the spBeta group use a small-molecule communication system to coordinate lysis-lysogeny decisions. During infection of its Bacillus host cell, the phage produces a 6aa communication peptide that is released to the medium. In subsequent infections, progeny phages measure the concentration of this peptide and lysogenize if the concentration is sufficiently high. We found that different phages encode different versions of the communication peptide, demonstrating a phage-specific peptide communication code for lysogeny decisions. We termed this communication system the “arbitrium” system, and further show that it is encoded by 3 phage genes: aimP, producing the peptide, aimR, the intracellular peptide receptor, and aimX, a negative regulator of lysogeny. The arbitrium system enables an offspring phage to communicate with its predecessors, i.e., to estimate the amount of recent prior infections and hence decide whether to employ the lytic or lysogenic cycle.

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Graphical Abstract Highlights d Arbitrium-like systems are common in phages infecting pathogens and soil bacteria d Peptide-based arbitrium communication regulates lysogeny in numerous phage types d Arbitrium systems are frequently encoded on mobile pathogenicity elements d A peptide-responsive non-coding RNA controls the regulator of the lysogenic state Authors Avigail Stokar-Avihail, Nitzan Tal, Zohar Erez, Anna Lopatina, Rotem Sorek Correspondence rotem.sorek@weizmann.ac.il In Brief Stokar-Avihail et al. discovered that numerous types of phages and mobile genetic elements encode peptide-based communication systems that guide lysogeny decisions. These elements infect many soil and pathogenic Bacilli. Peptide-based lysogeny decisions are likely executed by a non-coding RNA that controls the regulator of lysogeny. SUMMARY Temperate phages can adopt either a lytic or lysogenic lifestyle within their host bacteria. It was recently shown that Bacillus-subtilis-infecting phages of the SPbeta group utilize a peptide-based communication system called arbitrium to coordinate the lysogeny decision. The occurrence of peptide-based communication systems among phages more broadly remains to be explored. Here, we uncover a wide array of peptide-based communication systems utilized by phages for lysogeny decisions. These arbitrium-like systems show diverse peptide codes and can be detected in numerous genetically distant phage types and conjugative elements. The pathogens Bacillus anthracis, Bacillus cereus, andBacillus thuringiensis are commonly infected by arbitrium-carrying mobile elements, which often carry toxins essential for pathogenicity. Experiments with phages containing these arbitrium-like systems demonstrate their involvement in lysogeny decisions. Finally, our results suggest that the peptidebased decision is executed by an antisense RNA that controls the regulator of the lysogenic state.

Peroxisomes are ubiquitous and dynamic organelles that house many important pathways of cellular metabolism. In recent years it has been demonstrated that mitochondria are tightly connected with peroxisomes and are defective in several peroxisomal diseases. Indeed, these two organelles share metabolic routes as well as resident proteins and, at least in mammals, are connected via a vesicular transport pathway. However the exact extent of cross-talk between peroxisomes and mitochondria remains unclear. Here we used a combination of high throughput genetic manipulations of yeast libraries alongside high content screens to systematically unravel proteins that affect the transport of peroxisomal proteins and peroxisome biogenesis. Follow up work on the effector proteins that were identified revealed that peroxisomes are not randomly distributed in cells but are rather localized to specific mitochondrial subdomains such as mitochondria-ER junctions and sites of acetyl-CoA synthesis. Our approach highlights the intricate geography of the cell and suggests an additional layer of organization as a possible way to enable efficient metabolism. Our findings pave the way for further studying the machinery aligning mitochondria and peroxisomes, the role of the juxtaposition, as well as its regulation during various metabolic conditions. More broadly, the approaches used here can be easily applied to study any organelle of choice, facilitating the discovery of new aspects in cell biology.

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.

Bacterial anti-phage defense systems are frequently clustered in microbial genomes, forming defense islands. This genomic property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms in bacteria is still unknown. In this study we report the discovery of 21 new defense systems that protect bacteria from phages, based on computational genomic analyses and phage infection experiments. We find multiple systems with protein domains known to be involved in eukaryotic anti-viral immunity, including ISG15-like proteins, dynamin-like proteins, and SEFIR domains, and show that these domains participate in bacterial defense against phages. Additional systems include protein domains predicted to manipulate DNA and RNA molecules, as well as multiple toxin-antitoxin systems shown here to function in anti-phage defense. The systems we discovered are widely distributed in bacterial and archaeal genomes, and in some bacteria form a considerable fraction of the immune arsenal. Our data substantially expand the known inventory of defense systems utilized by bacteria to counteract phage infection.

This month: sage advice from phage to their offspring; systematic analyses of protein quality control, mitochondrial respiration, and woody biomass; a continental-scale experiment; and engineered protein tools galore.