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Nature Jan 2017Temperate viruses can become dormant in their host cells, a process called lysogeny. In every infection, such viruses decide between the lytic and the lysogenic cycles,...
Temperate viruses can become dormant in their host cells, a process called lysogeny. In every infection, such viruses decide between the lytic and the lysogenic cycles, that is, 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 six amino-acids-long communication peptide that is released into 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 term this communication system the 'arbitrium' system, and further show that it is encoded by three phage genes: aimP, which produces the peptide; aimR, the intracellular peptide receptor; and aimX, a negative regulator of lysogeny. The arbitrium system enables a descendant phage to 'communicate' with its predecessors, that is, to estimate the amount of recent previous infections and hence decide whether to employ the lytic or lysogenic cycle.
Topics: Amino Acid Sequence; Bacillus; Bacteriolysis; Bacteriophages; Culture Media, Conditioned; DNA, Viral; Lysogeny; Models, Biological; Peptides; Protein Multimerization; Transcription, Genetic; Viral Proteins
PubMed: 28099413
DOI: 10.1038/nature21049 -
Cell Jan 2019Vibrio cholerae uses a quorum-sensing (QS) system composed of the autoinducer 3,5-dimethylpyrazin-2-ol (DPO) and receptor VqmA (VqmA), which together repress genes for...
Vibrio cholerae uses a quorum-sensing (QS) system composed of the autoinducer 3,5-dimethylpyrazin-2-ol (DPO) and receptor VqmA (VqmA), which together repress genes for virulence and biofilm formation. vqmA genes exist in Vibrio and in one vibriophage, VP882. Phage-encoded VqmA (VqmA) binds to host-produced DPO, launching the phage lysis program via an antirepressor that inactivates the phage repressor by sequestration. The antirepressor interferes with repressors from related phages. Like phage VP882, these phages encode DNA-binding proteins and partner antirepressors, suggesting that they, too, integrate host-derived information into their lysis-lysogeny decisions. VqmA activates the host VqmA regulon, whereas VqmA cannot induce phage-mediated lysis, suggesting an asymmetry whereby the phage influences host QS while enacting its own lytic-lysogeny program without interference. We reprogram phages to activate lysis in response to user-defined cues. Our work shows that a phage, causing bacterial infections, and V. cholerae, causing human infections, rely on the same signal molecule for pathogenesis.
Topics: Bacteriophages; Biofilms; DNA-Binding Proteins; Gene Expression Regulation, Bacterial; Lysogeny; Pyrazoles; Quorum Sensing; Vibrio; Vibrio cholerae; Virulence; Virus Latency
PubMed: 30554875
DOI: 10.1016/j.cell.2018.10.059 -
Viruses Jan 2023Bacteriophages are ubiquitous organisms that can be specific to one or multiple strains of hosts, in addition to being the most abundant entities on the planet. It is... (Review)
Review
Bacteriophages are ubiquitous organisms that can be specific to one or multiple strains of hosts, in addition to being the most abundant entities on the planet. It is estimated that they exceed ten times the total number of bacteria. They are classified as temperate, which means that phages can integrate their genome into the host genome, originating a prophage that replicates with the host cell and may confer immunity against infection by the same type of phage; and lytics, those with greater biotechnological interest and are viruses that lyse the host cell at the end of its reproductive cycle. When lysogenic, they are capable of disseminating bacterial antibiotic resistance genes through horizontal gene transfer. When professionally lytic-that is, obligately lytic and not recently descended from a temperate ancestor-they become allies in bacterial control in ecological imbalance scenarios; these viruses have a biofilm-reducing capacity. Phage therapy has also been advocated by the scientific community, given the uniqueness of issues related to the control of microorganisms and biofilm production when compared to other commonly used techniques. The advantages of using bacteriophages appear as a viable and promising alternative. This review will provide updates on the landscape of phage applications for the biocontrol of pathogens in industrial settings and healthcare.
Topics: Bacteriophages; Prophages; Lysogeny; Biofilms; Biotechnology
PubMed: 36851563
DOI: 10.3390/v15020349 -
Bacteriological Reviews Dec 1953
Topics: Bacteriophages; Lysogeny
PubMed: 13105613
DOI: 10.1128/br.17.4.269-337.1953 -
Current Biology : CB Nov 2021Some Bacillus-infecting bacteriophages use a peptide-based communication system, termed arbitrium, to coordinate the lysis-lysogeny decision. In this system, the phage...
Some Bacillus-infecting bacteriophages use a peptide-based communication system, termed arbitrium, to coordinate the lysis-lysogeny decision. In this system, the phage produces AimP peptide during the lytic cycle. Once internalized by the host cell, AimP binds to the transcription factor AimR, reducing aimX expression and promoting lysogeny. Although these systems are present in a variety of mobile genetic elements, their role in the phage life cycle has only been characterized in phage phi3T during phage infection. Here, using the B. subtilis SPβ prophage, we show that the arbitrium system is also required for normal prophage induction. Deletion of the aimP gene increased phage reproduction, although the aimR deletion significantly reduced the number of phage particles produced after prophage induction. Moreover, our results indicated that AimR is involved in a complex network of regulation and brought forward two new players in the SPβ lysis-lysogeny decision system, YopN and the phage repressor YopR. Importantly, these proteins are encoded in an operon, the function of which is conserved across all SPβ-like phages encoding the arbitrium system. Finally, we obtained mutant phages in the arbitrium system, which behaved almost identically to the wild-type (WT) phage, indicating that the arbitrium system is not essential in the laboratory but is likely beneficial for phage fitness in nature. In support of this, by possessing a functional arbitrium system, the SPβ phage can optimize production of infective particles while also preserving the number of cells that survive after prophage induction, a strategy that increases phage persistence in nature.
Topics: Bacillus Phages; Bacteriophages; Lysogeny; Peptides; Virus Activation
PubMed: 34562384
DOI: 10.1016/j.cub.2021.08.072 -
Viruses May 2022Bacteriophages are obligatory parasites propagating in bacterial hosts in a lytic or lysogenic/pseudolysogenic cycle [...].
Bacteriophages are obligatory parasites propagating in bacterial hosts in a lytic or lysogenic/pseudolysogenic cycle [...].
Topics: Bacteria; Bacteriophages; Lysogeny
PubMed: 35632795
DOI: 10.3390/v14051054 -
Nature Communications Apr 2023Phage-plasmids are extra-chromosomal elements that act both as plasmids and as phages, whose eco-evolutionary dynamics remain poorly constrained. Here, we show that...
Phage-plasmids are extra-chromosomal elements that act both as plasmids and as phages, whose eco-evolutionary dynamics remain poorly constrained. Here, we show that segregational drift and loss-of-function mutations play key roles in the infection dynamics of a cosmopolitan phage-plasmid, allowing it to create continuous productive infections in a population of marine Roseobacter. Recurrent loss-of-function mutations in the phage repressor that controls prophage induction leads to constitutively lytic phage-plasmids that spread rapidly throughout the population. The entire phage-plasmid genome is packaged into virions, which were horizontally transferred by re-infecting lysogenized cells, leading to an increase in phage-plasmid copy number and to heterozygosity in a phage repressor locus in re-infected cells. However, the uneven distribution of phage-plasmids after cell division (i.e., segregational drift) leads to the production of offspring carrying only the constitutively lytic phage-plasmid, thus restarting the lysis-reinfection-segregation life cycle. Mathematical models and experiments show that these dynamics lead to a continuous productive infection of the bacterial population, in which lytic and lysogenic phage-plasmids coexist. Furthermore, analyses of marine bacterial genome sequences indicate that the plasmid backbone here can carry different phages and disseminates trans-continentally. Our study highlights how the interplay between phage infection and plasmid genetics provides a unique eco-evolutionary strategy for phage-plasmids.
Topics: Bacteriophages; Plasmids; Lysogeny; Virus Activation; Mutation
PubMed: 37041135
DOI: 10.1038/s41467-023-37512-x -
Open Biology Sep 2021The canonical lytic-lysogenic binary has been challenged in recent years, as more evidence has emerged on alternative bacteriophage infection strategies. These infection... (Review)
Review
The canonical lytic-lysogenic binary has been challenged in recent years, as more evidence has emerged on alternative bacteriophage infection strategies. These infection modes are little studied, and yet they appear to be more abundant and ubiquitous in nature than previously recognized, and can play a significant role in the ecology and evolution of their bacterial hosts. In this review, we discuss the extent, causes and consequences of alternative phage lifestyles, and clarify conceptual and terminological confusion to facilitate research progress. We propose distinct definitions for the terms 'pseudolysogeny' and 'productive or non-productive chronic infection', and distinguish them from the carrier state life cycle, which describes a population-level phenomenon. Our review also finds that phages may change their infection modes in response to environmental conditions or the physiological state of the host cell. We outline known molecular mechanisms underlying the alternative phage-host interactions, including specific genetic pathways and their considerable biotechnological potential. Moreover, we discuss potential implications of the alternative phage lifestyles for microbial biology and ecosystem functioning, as well as applied topics such as phage therapy.
Topics: Bacteria; Bacteriophages; Ecosystem; Lysogeny; Persistent Infection
PubMed: 34520699
DOI: 10.1098/rsob.210188 -
Nature Microbiology Jan 2024Phages can use a small-molecule communication arbitrium system to coordinate lysis-lysogeny decisions, but the underlying mechanism remains unknown. Here we determined...
Phages can use a small-molecule communication arbitrium system to coordinate lysis-lysogeny decisions, but the underlying mechanism remains unknown. Here we determined that the arbitrium system in Bacillus subtilis phage phi3T modulates the bacterial toxin-antitoxin system MazE-MazF to regulate the phage life cycle. We show that phi3T expresses AimX and YosL, which bind to and inactivate MazF. AimX also inhibits the function of phi3T_93, a protein that promotes lysogeny by binding to MazE and releasing MazF. Overall, these mutually exclusive interactions promote the lytic cycle of the phage. After several rounds of infection, the phage-encoded AimP peptide accumulates intracellularly and inactivates the phage antiterminator AimR, a process that eliminates aimX expression from the aimP promoter. Therefore, when AimP increases, MazF activity promotes reversion back to lysogeny, since AimX is absent. Altogether, our study reveals the evolutionary strategy used by arbitrium to control lysis-lysogeny by domesticating and fine-tuning a phage-defence mechanism.
Topics: Lysogeny; Bacillus Phages; Peptides; Cell Death
PubMed: 38177302
DOI: 10.1038/s41564-023-01550-4 -
The Journal of Biological Chemistry Mar 2019Cellular decision-making guides complex development such as cell differentiation and disease progression. Much of our knowledge about decision-making is derived from... (Review)
Review
Cellular decision-making guides complex development such as cell differentiation and disease progression. Much of our knowledge about decision-making is derived from simple models, such as bacteriophage lambda infection, in which lambda chooses between the vegetative lytic fate and the dormant lysogenic fate. This paradigmatic system is broadly understood but lacking mechanistic details, partly due to limited resolution of past studies. Here, we discuss how modern technologies have enabled high-resolution examination of lambda decision-making to provide new insights and exciting possibilities in studying this classical system. The advent of techniques for labeling specific DNA, RNA, and proteins in cells allows for molecular-level characterization of events in lambda development. These capabilities yield both new answers and new questions regarding how the isolated lambda genetic circuit acts, what biological events transpire among phages in their natural context, and how the synergy of simple phage macromolecules brings about complex behaviors.
Topics: Bacteriophage lambda; DNA, Viral; Lysogeny; RNA, Viral
PubMed: 30242122
DOI: 10.1074/jbc.TM118.003209