Temperate Phage Research Articles

Comprehensive Characterization of a Streptococcus agalactiae Phage Isolated from a Tilapia Farm in Selangor, Malaysia, and Its Potential for Phage Therapy.

The Streptococcus agalactiae outbreak in tilapia has caused huge losses in the aquaculture industry worldwide. In Malaysia, several studies have reported the isolation of S. agalactiae, but no study has reported the isolation of S. agalactiae phages from tilapia or from the culture pond. Here, the isolation of the S. agalactiae phage from infected tilapia is reported and it is named as vB_Sags-UPM1. Transmission electron micrograph (TEM) revealed that this phage showed characteristics of a Siphoviridae and it was able to kill two local S. agalactiae isolates, which were S. agalactiae smyh01 and smyh02. Whole genome sequencing (WGS) of the phage DNA showed that it contained 42,999 base pairs with 36.80% GC content. Bioinformatics analysis predicted that this phage shared an identity with the S. agalactiae S73 chromosome as well as several other strains of S. agalactiae, presumably due to prophages carried by these hosts, and it encodes integrase, which suggests that it was a temperate phage. The endolysin of vB_Sags-UPM1 termed Lys60 showed killing activity on both S. agalactiae strains with varying efficacy. The discovery of the S. agalactiae temperate phage and its antimicrobial genes could open a new window for the development of antimicrobials to treat S. agalactiae infection.

Characterization of Temperate LPS-Binding Bordetella avium Phages That Lack Superinfection Immunity.

Bordetella avium causes a highly infectious upper respiratory tract disease in turkeys and other poultry with high economic losses. Considering the antimicrobial resistance crisis, bacteriophages (phages) may be an alternative approach for treating bacterial infections such as bordetellosis. Here, we describe seven B. avium phages, isolated from drinking water and feces from chicken and turkey farms. They showed strong bacteriolytic activity with a broad host range and used lipopolysaccharides (LPS) as a host receptor for their adsorption. All phages are myoviruses based on their structure observed by transmission electron microscopy. Genome sequence analyses revealed genome assembly sizes ranging from 39,087 to 43,144 bp. Their permutated genomes were organized colinearly, with a conserved module order, and were packed according to a predicted headful packing strategy. Notably, they contained genes encoding putative markers of lysogeny, indicative of temperate phages, despite their lytic phenotype. Further investigation revealed that the phages could indeed undergo a lysogenic life cycle with varying frequency. However, the lysogenic bacteria were still susceptible to superinfection with the same phages. This lack of stable superinfection immunity after lysogenization appears to be a characteristic feature of B. avium phages, which is favorable in terms of a potential therapeutic use of phages for the treatment of avian bordetellosis. IMPORTANCE To maintain the effectiveness of antibiotics over the long term, alternatives to treat infectious diseases are urgently needed. Therefore, phages have recently come back into focus as they can specifically infect and lyse bacteria and are naturally occurring. However, there is little information on phages that can infect pathogenic bacteria from animals, such as the causative agent of bordetellosis of poultry, B. avium. Therefore, in this study, B. avium phages were isolated and comprehensively characterized, including whole-genome analysis. Although phenotypically the phages were thought to undergo a lytic cycle, we demonstrated that they undergo a lysogenic phase, but that infection does not confer stable host superinfection immunity. These findings provide important information that could be relevant for potential biocontrol of avian bordetellosis by using phage therapy.

Temperate phage influence virulence and biofilm-forming of Salmonella Typhimurium and enhance the ability to contaminate food product

Salmonella is a food-borne zoonotic pathogen that threatens food safety and public health security. Temperate phages can influence bacterial virulence and phenotype and play an important role in bacterial evolution. However, most studies on Salmonella temperate phages focus on prophage induced by bacteria, with few reports on Salmonella temperate phages isolated in the environment. Moreover, whether temperate phages drive bacterial virulence and biofilm formation in food and animal models remains unknown. In this study, Salmonella temperate phage vB_Sal_PHB48 was isolated from sewage. TEM and phylogenetic analysis indicated that phage PHB48 belongs to the Myoviridae family. Additionally, Salmonella Typhimurium integrating PHB48 was screened and designated as Sal013+. Whole genome sequencing revealed that the integration site was specific and we confirmed that the integration of PHB48 did not change the O-antigen and coding sequences of Sal013. Our in vitro and in vivo studies showed that the integration of PHB48 could significantly enhance the virulence and biofilm formation of S. Typhimurium. More importantly, the integration of PHB48 significantly improved the colonization and contamination ability of bacteria in food samples. In conclusion, we isolated Salmonella temperate phage directly from the environment and systematically clarified that PHB48 enhanced the virulence and biofilm-forming ability of Salmonella. In addition, we found that PHB48 increased the colonization and contamination ability of Salmonella in food samples. These results indicated that the highly pathogenic Salmonella induced by temperate phage was more harmful to food matrices and public health security. Our results could enhance the understanding of the evolutionary relationship between bacteriophages and bacteria, and raise public awareness of large-scale outbreaks resulting from Salmonella virulence enhancement in food industry.

Antidepressants amitriptyline, fluoxetine, and traditional Chinese medicine Xiaoyaosan caused alterations in gut DNA virome composition and function in rats exposed chronic unpredictable mild stress.

In clinical practice, antidepressant drugs are widely used to treat depression. Previous studies have attention to the impact of antidepressants on the bacterial microbiome, while the role of these drugs in the gut virome is still unclear. In this study, we estimated the effects of antidepressant amitriptyline (Ami), fluoxetine (Flu), and traditional Chinese medicine Xiaoyaosan (XYS) administration on gut viral composition and function in a chronic unpredictable mild stress (CUMS)-induced depression rat model based on shotgun metagenomic sequencing. The results showed that treatment with Ami, Flu, and XYS significantly changed the gut viral composition compared with the CUMS-induced rats. At the family level, the abundance of f_unclassified_Caudovirales in CUMS rats was remarkably lower than in the HC rats, nevertheless, XYS significantly recovered the abundance of Caudovirales. Meanwhile, the abundance of Podoviridae was expanded in CUMS rats compared with the HC rats, and the profile was then significantly reduced after XYS treatment. Furthermore, both antidepressants and XYS increased the abundance of Siphoviridae compared with the CUMS rats, but only Ami treatments had significant differences. Subsequent function annotation further implied that Ami, Flu, and XYS showed to involve an alteration of the diverse viral functions, such as carbohydrate metabolism, xenobiotics biodegradation and metabolism, community-prokaryotes, translation, and neurodegenerative disease. Additionally, the co-occurrence network displayed that there are complex interactions between viral operational taxonomic units (vOTUs) represented by temperate phages and the majority of bacterial genera in the intestine ecosystem. Our study proved for the first time that depression is characterized by massive alterations and functional distortion of the gut viruses, and after oral administration of Ami, Flu, and XYS could affect disordered gut virome, which could be a novel target in depression.

Coliphages of the human urinary microbiota.

Due to its frequent association with urinary tract infections (UTIs), Escherichia coli is the best characterized constituent of the urinary microbiota (urobiome). However, uropathogenic E. coli is just one member of the urobiome. In addition to bacterial constituents, the urobiome of both healthy and symptomatic individuals is home to a diverse population of bacterial viruses (bacteriophages). A prior investigation found that most bacterial species in the urobiome are lysogens, harboring one or more phages integrated into their genome (prophages). Many of these prophages are temperate phages, capable of entering the lytic cycle and thus lysing their bacterial host. This transition from the lysogenic to lytic life cycle can impact the bacterial diversity of the urobiome. While many phages that infect E. coli (coliphages) have been studied for decades in the laboratory setting, the coliphages within the urobiome have yet to be cataloged. Here, we investigated the diversity of urinary coliphages by first identifying prophages in all publicly available urinary E. coli genomes. We detected 3,038 intact prophage sequences, representative of 1,542 unique phages. These phages include both novel species as well as species also found within the gut microbiota. Ten temperate phages were isolated from urinary E. coli strains included in our analysis, and we assessed their ability to infect and lyse urinary E. coli strains. We also included in these host range assays other urinary coliphages and laboratory coliphages. The temperate phages and other urinary coliphages were successful in lysing urinary E. coli strains. We also observed that coliphages from non-urinary sources were most efficient in killing urinary E. coli strains. The two phages, T2 and N4, were capable of lysing 83.5% (n = 86) of strains isolated from females with UTI symptoms. In conclusion, our study finds a diverse community of coliphages in the urobiome, many of which are predicted to be temperate phages, ten of which were confirmed here. Their ability to infect and lyse urinary E. coli strains suggests that urinary coliphages may play a role in modulating the E. coli strain diversity of the urobiome.

Expanding known viral diversity in the healthy infant gut

The gut microbiome is shaped through infancy and impacts the maturation of the immune system, thus protecting against chronic disease later in life. Phages, or viruses that infect bacteria, modulate bacterial growth by lysis and lysogeny, with the latter being especially prominent in the infant gut. Viral metagenomes (viromes) are difficult to analyse because they span uncharted viral diversity, lacking marker genes and standardized detection methods. Here we systematically resolved the viral diversity in faecal viromes from 647 1-year-olds belonging to Copenhagen Prospective Studies on Asthma in Childhood 2010, an unselected Danish cohort of healthy mother–child pairs. By assembly and curation we uncovered 10,000 viral species from 248 virus family-level clades (VFCs). Most (232 VFCs) were previously unknown, belonging to the Caudoviricetes viral class. Hosts were determined for 79% of phage using clustered regularly interspaced short palindromic repeat spacers within bacterial metagenomes from the same children. Typical Bacteroides-infecting crAssphages were outnumbered by undescribed phage families infecting Clostridiales and Bifidobacterium. Phage lifestyles were conserved at the viral family level, with 33 virulent and 118 temperate phage families. Virulent phages were more abundant, while temperate ones were more prevalent and diverse. Together, the viral families found in this study expand existing phage taxonomy and provide a resource aiding future infant gut virome research.

Temperate bacteriophages infecting the mucin-degrading bacterium Ruminococcus gnavus from the human gut

ABSTRACT Ruminococcus gnavus is a prevalent gut microbe reported to occur in higher abundance among individuals with inflammatory bowel disease (IBD). This study reports the isolation and characterization of six bacteriophages (phages) isolated from human fecal material and environmental samples that infect this species. Isolated phages have a siphovirus morphology, with genomes ranging between 36.5 and 37.8 kbp. Genome analysis indicates that the phages have a temperate lifestyle, which was confirmed by their ability to form lysogens on their host bacterial species. In contrast to the finding that phages lyse their host in liquid medium, results from a mouse trial indicate these phages can co-exist with the host bacterium in the gut without causing a significant reduction of R. gnavus. The bacterial counts in the feces of phage-treated mice did not significantly differ in the presence of phage. Furthermore, analysis of publicly available gut virome sequence data indicates a high abundance of these phages among individuals suffering from IBD. This work provides the first insight into how phages interact with R. gnavus in the human gut microbiome.

Efficient traceless modification of the P1 bacteriophage genome through homologous recombination with enrichment in double recombinants: A new perspective on the functional annotation of uncharacterized phage genes.

The advent of high-throughput omic technologies has caused unprecedented progress in research on bacteriophages, the most abundant and still the least explored entities on earth. Despite the growing number of phage genomes sequenced and the rejuvenation of interest in phage therapy, the progress in the functional analysis of phage genes is slow. Simple and efficient techniques of phage genome targeted mutagenesis that would allow one to knock out particular genes precisely without polar effects in order to study the effect of these knock-outs on phage functions are lacking. Even in the case of model phages, the functions of approximately half of their genes are unknown. P1 is an enterobacterial temperate myophage of clinical significance, which lysogenizes cells as a plasmid. It has a long history of studies, serves as a model in basic research, is a gene transfer vector, and is a source of genetic tools. Its gene products have structural homologs in several other phages. In this perspective article, we describe a simple and efficient procedure of traceless P1 genome modification that could also serve to acquire targeted mutations in the genomes of certain other temperate phages and speed up functional annotations of phage genes.

Large-scale identification of known and novel RRNPP quorum sensing systems by RRNPP_detector captures novel features of bacterial, plasmidic and viral co-evolution.

Gram-positive Firmicutes bacteria and their mobile genetic elements (plasmids, bacteriophages) encode peptide-based quorum sensing systems (QSSs) that orchestrate behavioral transitions as a function of population densities. In their simplest form, termed "RRNPP", these QSSs are composed of two adjacent genes: a communication propeptide and its cognate intracellular receptor. RRNPP QSSs notably regulate social/competitive behaviors such as virulence or biofilm formation in bacteria, conjugation in plasmids or lysogeny in temperate bacteriophages. However, the genetic diversity and the prevalence of these communication systems, together with the breadth of behaviors they control, remain largely under-appreciated. To better assess the impact of density-dependency on microbial community dynamics and evolution, we developed the RRNPP_detector software, which predicts known and novel RRNPP QSSs in chromosomes, plasmids and bacteriophages of Firmicutes. Applying RRNPP_detector against available complete genomes of viruses and Firmicutes, we identified a rich repertoire of RRNPP QSSs from 11 already-known subfamilies and 21 novel high-confidence candidate subfamilies distributed across a vast diversity of taxa. The analysis of high-confidence RRNPP subfamilies notably revealed 14 subfamilies shared between chromosomes/plasmids/phages, 181 plasmids and 82 phages encoding multiple communication systems, phage-encoded QSSs predicted to dynamically modulate bacterial behaviors, and 196 candidate biosynthetic gene clusters under density-dependent regulation. Overall, our work enhances the field of quorum sensing research and reveals novel insights into the co-evolution of gram-positive bacteria and their mobile genetic elements.

The book of Lambda does not tell us that naturally occurring lysogens of Escherichia coli are likely to be resistant as well as immune

The most significant difference between bacteriophages functionally and ecologically is whether they are purely lytic (virulent) or temperate. Virulent phages can only be transmitted horizontally by infection, most commonly with the death of their hosts. Temperate phages can also be transmitted horizontally, but upon infection of susceptible bacteria, their genomes can be incorporated into that of their host's as a prophage and be transmitted vertically in the course of cell division by their lysogenic hosts. From what we know from studies with the temperate phage Lambda and other temperate phages, in laboratory culture, lysogenic bacteria are protected from killing by the phage coded for by their prophage by immunity; where upon infecting lysogens, the free temperate phage coded by their prophage is lost. Why are lysogens not only resistant but also immune to the phage coded by their prophage since immunity does not confer protection against virulent phages? To address this question, we used a mathematical model and performed experiments with temperate and virulent mutants of the phage Lambda in laboratory culture. Our models predict and experiments confirm that selection would favor the evolution of resistant and immune lysogens, particularly if the environment includes virulent phage that shares the same receptors as the temperate. To explore the validity and generality of this prediction, we examined 10 lysogenic Escherichia coli from natural populations. All 10 were capable of forming immune lysogens, but their original hosts were resistant to the phage coded by their prophage.

Multiomic spatial analysis reveals a distinct mucosa-associated virome

ABSTRACT The human gut virome has been increasingly explored in recent years. However, nearly all virome-sequencing efforts rely solely on fecal samples and few studies leverage multiomic approaches to investigate phage–host relationships. Here, we combine metagenomics, metaviromics, and metatranscriptomics to study virome-bacteriome interactions at the colonic mucosal-luminal interface in a cohort of three individuals with inflammatory bowel disease; non-IBD controls were not included in this study. We show that the mucosal viral population is distinct from the stool virome and houses abundant crAss-like phages that are undetectable by fecal sampling. Through viral protein prediction and metatranscriptomic analysis, we explore viral gene transcription, prophage activation, and the relationship between the presence of integrase and temperate phages in IBD subjects. We also show the impact of deep sequencing on virus recovery and offer guidelines for selecting optimal sequencing depths in future metaviromic studies. Systems biology approaches such as those presented in this report will enhance our understanding of the human virome and its interactions with our microbiome and our health.

Whole-Genome Sequences of a Lactobacillus melliventris Strain and Its Myovirus Temperate Phage, phIBH004, Isolated from the Digestive Tract of Apis mellifera in Switzerland.

The complete genome sequence of Lactobacillus melliventris strain IBH004, isolated from the gut of a honeybee worker (Apis mellifera) and containing two plasmids and a temperate phage, was determined using hybrid assembly of Oxford Nanopore and Illumina reads. Phage-sequence relationships were identified from the coding sequences, and a proteomic tree was constructed.

The Role of Temperate Phages in Bacterial Pathogenicity.

Bacteriophages are viruses that infect bacteria and archaea and are classified as virulent or temperate phages based on their life cycles. A temperate phage, also known as a lysogenic phage, integrates its genomes into host bacterial chromosomes as a prophage. Previous studies have indicated that temperate phages are beneficial to their susceptible bacterial hosts by introducing additional genes to bacterial chromosomes, creating a mutually beneficial relationship. This article reviewed three primary ways temperate phages contribute to the bacterial pathogenicity of foodborne pathogens, including phage-mediated virulence gene transfer, antibiotic resistance gene mobilization, and biofilm formation. This study provides insights into mechanisms of phage-bacterium interactions in the context of foodborne pathogens and provokes new considerations for further research to avoid the potential of phage-mediated harmful gene transfer in agricultural environments.

Staying below the Radar: Unraveling a New Family of Ubiquitous "Cryptic" Non-Tailed Temperate Vibriophages and Implications for Their Bacterial Hosts.

Bacteriophages are the most abundant biological entities in the oceans and play key roles in bacterial activity, diversity and evolution. While extensive research has been conducted on the role of tailed viruses (Class: Caudoviricetes), very little is known about the distribution and functions of the non-tailed viruses (Class: Tectiliviricetes). The recent discovery of the lytic Autolykiviridae family demonstrated the potential importance of this structural lineage, emphasizing the need for further exploration of the role of this group of marine viruses. Here, we report the novel family of temperate phages under the class of Tectiliviricetes, which we propose to name "Asemoviridae" with phage NO16 as a main representative. These phages are widely distributed across geographical regions and isolation sources and found inside the genomes of at least 30 species of Vibrio, in addition to the original V. anguillarum isolation host. Genomic analysis identified dif-like sites, suggesting that NO16 prophages recombine with the bacterial genome based on the XerCD site-specific recombination mechanism. The interactions between the NO16 phage and its V. anguillarum host were linked to cell density and phage-host ratio. High cell density and low phage predation levels were shown to favor the temperate over the lytic lifestyle for NO16 viruses, and their spontaneous induction rate was highly variable between different V. anguillarum lysogenic strains. NO16 prophages coexist with the V. anguillarum host in a mutualistic interaction by rendering fitness properties to the host, such as increased virulence and biofilm formation through lysogenic conversion, likely contributing to their global distribution.

Complete Genome Sequence of the Lysogenic Pseudomonas Bacteriophage Fyn8.

A temperate bacteriophage infecting Pseudomonas aeruginosa PAO1 was isolated from river water. Nanopore sequencing revealed that it has a circular double-stranded DNA genome of 45,617 bp, containing typical phage structural proteins and lambda-like lysogeny regulators. Putative O-antigen serotype conversion and anti-cyclic oligonucleotide-based antiphage signaling system (CBASS) defense system proteins were also identified.

Interspecies Horizontal Transfer and Specific Integration of the Mosquitocidal Toxin-Encoding Plasmid pTAND672-2 from Bacillus thuringiensis subsp. israelensis to Lysinibacillus sphaericus.

pTAND672-2, a 144-kb resident plasmid of Bacillus thuringiensis serovar israelensis strain TAND672, was sequenced and characterized. This extrachromosomal element carries mosquitocidal toxin-, conjugation-, and recombinase-encoding genes, together with a putative arbitrium system, a genetic module recently discovered in temperate phages controlling lysogeny-lysis transition and in mobile genetic elements (MGEs) where its function remains clarified. Using conjugation experiments, pTAND672-2 is shown to be a novel integrative and conjugative element (ICE), which can horizontally transfer from B. thuringiensis serovar israelensis to Lysinibacillus sphaericus, another mosquitocidal bacterium, where it integrates into the chromosome. Its integration and circularization are reversible and involve a single-cross recombination between 33-bp specific sites, attB in the chromosome of L. sphaericus and attP in pTAND672-2. CDS143, coding for the putative tyrosine integrase Int143 distantly related to site-specific tyrosine Xer recombinases and phage integrases, can mediate the integration of pTAND672-2 to attB. The B. thuringiensis mosquito-killing genes carried by pTAND672-2 are efficiently transcribed and expressed in L. sphaericus, displaying a slight increased toxicity in this bacterium against Aedes albopictus larvae. The occurrence of pTAND672-2-like plasmids within the Bacillus cereus group was also explored and indicated that they all share a similar genetic backbone with diverse plasmid sizes, ranging from 58 to 225 kb. Interestingly, among them, the pEFR-4-4 plasmid of Bacillus paranthracis EFR-4 and p5 of B. thuringiensis BT-59 also display conjugative capability; moreover, like pTAND672-2 displays a chimeric structure between the pCH_133-e- and pBtoxis-like plasmids, pBTHD789-3 also appears to be mosaic of two plasmids. IMPORTANCE Horizontal transfer of mobile genetic elements carrying mosquitocidal toxin genes may play a driving role in the diversity of mosquitocidal bacteria. Here, the 144-kb mosquitocidal toxin-encoding plasmid pTAND672-2 is the first verified integrative and conjugative element (ICE) identified in Bacillus thuringiensis serovar israelensis. The key tyrosine integrase Int143, involved in the specific integration, is distantly related to other tyrosine recombinases. The study also reports the occurrence and potential interspecies transmission of pTAND672-2-like plasmids with varied sizes in B. thuringiensis, Bacillus paranthracis, and Bacillus wiedmannii isolates belonging to the Bacillus cereus group. This study is important for further understanding the evolution and ecology of mosquitocidal bacteria, as well as for providing new direction for the genetic engineering of biopesticides in the control of disease-transmitting mosquitoes.

Microbial density-dependent viral dynamics and low activity of temperate phages in the activated sludge process

The ecological behavior of bacteriophages (phages), the most abundant biological entity in wastewater treatment systems, is poorly understood, especially that of temperate phages. Here, the temporal dynamics of lytic and temperate phages in a laboratory-scale activated sludge reactor with a sludge bulking issue was investigated using coupled sludge metagenomic and viromic analyses. The lysogenic fragments (prophages) identified were widely distributed in the reconstructed metagenome-assembled genomes (61.7%, n = 227). However, only 12.3% of the identified prophages experienced lysogenic-lytic switching, and the abundance contribution of prophages to free virus communities was only 0.02–0.3%, indicating low activity of temperate phages. Although the sludge community changed dramatically during reactor operation, no massive prophage induction events were detected. Statistical analyses showed strong correlations between sludge concentration and free virus and temperate phage communities, suggesting microbial density-dependent virus dynamics in the sludge microbiota.

Transcriptional analysis in bacteriophage Fc02 of Pseudomonas aeruginosa revealed two overlapping genes with exclusion activity.

Little is known about the gene expression program during the transition from lysogenic to lytic cycles of temperate bacteriophages in Pseudomonas aeruginosa. To investigate this issue, we developed a thermo-sensitive repressor mutant in a lysogen and analyzed the phage transcriptional program by strand-specific RNA-Seq before and after thermo-induction. As expected, the repressor gene located on the phage DNA forward strand is transcribed in the lysogen at the permissive temperature of 30°C. Upstream the repressor gene, we noticed the presence of two overlapped ORFs apparently in the same transcript. One ORF is a gene that encodes a protein of 7.9 kDa mediating the exclusion of various super-infecting phages. The other ORF, placed in an alternate reading frame with a possible AUG initiation codon at 25 nucleotide downstream of the AUG of the first gene, is expected to encode a 20.7 kDa polypeptide of yet an unknown function. Upon lifting repression at 40°C, the transcription of an operon which is involved in the lytic cycle is started from a promoter on the reverse phage DNA strand. The first gene in the operon is a homolog of the antirepresor ner, a common gene in the lysis-lysogeny regulation region of other phages. Interestingly, the next gene after ner is gene 10 that on the reverse strand overlaps the overlapped gene olg1 on the forward strand. Curiously, gene 10 expression also shows superinfection exclusion. Strand-specific RNA-Seq also has uncovered the transcription succession of gene modules expressed during the phage lytic stage. The conservation of overlapped genes with similar functions may be evolutionarily selected.

Disarm The Bacteria: What Temperate Phages Can Do.

In the field of phage applications and clinical treatment, virulent phages have been in the spotlight whereas temperate phages received, relatively speaking, less attention. The fact that temperate phages often carry virulent or drug-resistant genes is a constant concern and drawback in temperate phage applications. However, temperate phages also play a role in bacterial regulation. This review elucidates the biological properties of temperate phages based on their life cycle and introduces the latest work on temperate phage applications, such as on host virulence reduction, biofilm degradation, genetic engineering and phage display. The versatile use of temperate phages coupled with their inherent properties, such as economy, ready accessibility, wide variety and host specificity, make temperate phages a solid candidate in tackling bacterial infections.

Current landscape on phage therapy in infections: time to leave it behind for good?

Bacteriophages (or phages) are viruses that infect and replicate within bacteria and it is believed they are the most abundant organisms in Earth.1 The lytic cycle of the phage, which results in replication and bacterial lysis, can occur immediately after infection (virulent phages) or the phage can integrate into the bacterium’s genome resulting in a lysogenic phage that may eventually evolve into a lytic cycle (temperate phages).2 Bacteria-phage coevolution shapes complex ecosystems, maintaining phenotypic and genetic diversity and increasing the rate of bacterial and phage evolution and divergence.