-
MSystems Oct 2023species include several human pathogens and mycobacteriophages show potential for therapeutic use to control infections. However, phage infection profiles vary greatly...
species include several human pathogens and mycobacteriophages show potential for therapeutic use to control infections. However, phage infection profiles vary greatly among clinical isolates and phage therapies must be personalized for individual patients. phage susceptibility is likely determined primarily by accessory parts of bacterial genomes, and we have identified the prophage and phage-related genomic regions across sequenced strains. The prophages are numerous and diverse, especially in genomes, and provide a potentially rich reservoir of new viruses that can be propagated lytically and used to expand the repertoire of therapeutically useful phages.
Topics: Humans; Prophages; Mycobacterium; Bacteriophages; Mycobacteriophages; Genome, Bacterial
PubMed: 37791767
DOI: 10.1128/msystems.00446-23 -
Viruses May 2018In this article we explain how current events in the field of phage therapy may positively influence its future development. We discuss the shift in position of the... (Review)
Review
In this article we explain how current events in the field of phage therapy may positively influence its future development. We discuss the shift in position of the authorities, academia, media, non-governmental organizations, regulatory agencies, patients, and doctors which could enable further advances in the research and application of the therapy. In addition, we discuss methods to obtain optimal phage preparations and suggest the potential of novel applications of phage therapy extending beyond its anti-bacterial action.
Topics: Animals; Bacteria; Bacteriophages; Clinical Trials as Topic; Humans; Immunomodulation; Mice; Phage Therapy; Prophages
PubMed: 29843391
DOI: 10.3390/v10060288 -
Microbiology (Reading, England) Mar 2018DNases are abundant among the pathogenic streptococci, with most species harbouring genes for at least one. Despite their prevalence, however, the role for these... (Review)
Review
DNases are abundant among the pathogenic streptococci, with most species harbouring genes for at least one. Despite their prevalence, however, the role for these extracellular enzymes is still relatively unclear. The DNases of the Lancefield group A Streptococcus, S. pyogenes are the best characterized, with a total of eight DNase genes identified so far. Six are known to be associated with integrated prophages. Two are chromosomally encoded, and one of these is cell-wall anchored. Homologues of both prophage-associated and chromosomally encoded S. pyogenes DNases have been identified in other streptococcal species, as well as other unique DNases. A major role identified for streptococcal DNases appears to be in the destruction of extracellular traps produced by immune cells, such as neutrophils, to ensnare bacteria and kill them. These traps are composed primarily of DNA which can be degraded by the secreted and cell-wall-anchored streptococcal DNases. DNases can also reduce TLR-9 signalling to dampen the immune response and produce cytotoxic deoxyadenosine to limit phagocytosis. Upper respiratory tract infection models of S. pyogenes have identified a role for DNases in potentiating infection and transmission, possibly by limiting the immune response or through some other unknown mechanism. Streptococcal DNases may also be involved in interacting with other microbial communities through communication, bacterial killing and disruption of competitive biofilms, or control of their own biofilm production. The contribution of DNases to pathogenesis may therefore be wide ranging and extend beyond direct interference with the host immune response.
Topics: Bacterial Proteins; Deoxyribonucleases; Extracellular Traps; Host-Pathogen Interactions; Humans; Immune Evasion; Microbial Interactions; Prophages; Streptococcal Infections; Streptococcus pyogenes
PubMed: 29458565
DOI: 10.1099/mic.0.000612 -
Microbiology Spectrum Jul 2018The study of bacteriophages (phages) and prophages has provided key insights into almost every cellular process as well as led to the discovery of unexpected new... (Review)
Review
The study of bacteriophages (phages) and prophages has provided key insights into almost every cellular process as well as led to the discovery of unexpected new mechanisms and the development of valuable tools. This is exemplified for RNA-based regulation. For instance, the characterization and exploitation of the antiphage CRISPR (clustered regularly interspaced short palindromic repeat) systems is revolutionizing molecular biology. Phage-encoded proteins such as the RNA-binding MS2 protein, which is broadly used to isolate tagged RNAs, also have been developed as valuable tools. Hfq, the RNA chaperone protein central to the function of many base-pairing small RNAs (sRNAs), was first characterized as a bacterial host factor required for Qβ phage replication. The ongoing studies of RNAs are continuing to reveal regulatory connections between infecting phages, prophages, and bacteria and to provide novel insights. There are bacterial and prophage sRNAs that regulate prophage genes, which impact bacterial virulence as well as bacterial cell killing. Conversely, phage- and prophage-encoded sRNAs modulate the expression of bacterial genes modifying metabolism. An interesting subcategory of the prophage-encoded sRNAs are sponge RNAs that inhibit the activities of bacterial-encoded sRNAs. Phages also affect posttranscriptional regulation in bacteria through proteins that inhibit or alter the activities of key bacterial proteins involved in posttranscriptional regulation. However, what is most exciting about phage and prophage research, given the millions of phage-encoded genes that have not yet been characterized, is the vast potential for discovering new RNA regulators and novel mechanisms and for gaining insight into the evolution of regulatory RNAs.
Topics: Bacteria; Bacterial Proteins; Bacterial Toxins; Bacteriophages; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Viral; Genes, Bacterial; Genome, Bacterial; Host-Pathogen Interactions; Prophages; RNA, Bacterial; RNA-Binding Proteins; Viral Proteins; Virulence; Virus Replication
PubMed: 30006994
DOI: 10.1128/microbiolspec.RWR-0027-2018 -
Science (New York, N.Y.) Mar 2024The extent to which prophage proteins interact with eukaryotic macromolecules is largely unknown. In this work, we show that cytoplasmic incompatibility factor A (CifA)...
The extent to which prophage proteins interact with eukaryotic macromolecules is largely unknown. In this work, we show that cytoplasmic incompatibility factor A (CifA) and B (CifB) proteins, encoded by prophage WO of the endosymbiont alter long noncoding RNA (lncRNA) and DNA during sperm development to establish a paternal-effect embryonic lethality known as cytoplasmic incompatibility (CI). CifA is a ribonuclease (RNase) that depletes a spermatocyte lncRNA important for the histone-to-protamine transition of spermiogenesis. Both CifA and CifB are deoxyribonucleases (DNases) that elevate DNA damage in late spermiogenesis. lncRNA knockdown enhances CI, and mutagenesis links lncRNA depletion and subsequent sperm chromatin integrity changes to embryonic DNA damage and CI. Hence, prophage proteins interact with eukaryotic macromolecules during gametogenesis to create a symbiosis that is fundamental to insect evolution and vector control.
Topics: Animals; Male; Cytoplasm; DNA; Prophages; RNA, Long Noncoding; Spermatozoa; Wolbachia; Paternal Inheritance; Viral Proteins; Drosophila melanogaster; Bacterial Proteins; Deoxyribonucleases
PubMed: 38452081
DOI: 10.1126/science.adk9469 -
Drug Resistance Updates : Reviews and... Jul 2016Bacterial chromosomes may contain up to 20% phage DNA that encodes diverse proteins ranging from those for photosynthesis to those for autoimmunity; hence, phages... (Review)
Review
Bacterial chromosomes may contain up to 20% phage DNA that encodes diverse proteins ranging from those for photosynthesis to those for autoimmunity; hence, phages contribute greatly to the metabolic potential of pathogens. Active prophages carrying genes encoding virulence factors and antibiotic resistance can be excised from the host chromosome to form active phages and are transmissible among different bacterial hosts upon SOS responses. Cryptic prophages are artifacts of mutagenesis in which lysogenic phage are captured in the bacterial chromosome: they may excise but they do not form active phage particles or lyse their captors. Hence, cryptic prophages are relatively permanent reservoirs of genes, many of which benefit pathogens, in ways we are just beginning to discern. Here we explore the role of active prophage- and cryptic prophage-derived proteins in terms of (i) virulence, (ii) antibiotic resistance, and (iii) antibiotic tolerance; antibiotic tolerance occurs as a result of the non-heritable phenotype of dormancy which is a result of activation of toxins of toxin/antitoxin loci that are frequently encoded in cryptic prophages. Therefore, cryptic prophages are promising targets for drug development.
Topics: Anti-Bacterial Agents; Bacteria; Chromosomes, Bacterial; Drug Resistance, Microbial; Gene Transfer, Horizontal; Genome, Bacterial; Lysogeny; Prophages; SOS Response, Genetics; Toxin-Antitoxin Systems; Virulence; Virulence Factors
PubMed: 27449596
DOI: 10.1016/j.drup.2016.06.001 -
Nucleic Acids Research Jul 2023PHASTEST (PHAge Search Tool with Enhanced Sequence Translation) is the successor to the PHAST and PHASTER prophage finding web servers. PHASTEST is designed to support...
PHASTEST (PHAge Search Tool with Enhanced Sequence Translation) is the successor to the PHAST and PHASTER prophage finding web servers. PHASTEST is designed to support the rapid identification, annotation and visualization of prophage sequences within bacterial genomes and plasmids. PHASTEST also supports rapid annotation and interactive visualization of all other genes (protein coding regions, tRNA/tmRNA/rRNA sequences) in bacterial genomes. Given that bacterial genome sequencing has become so routine, the need for fast tools to comprehensively annotate bacterial genomes has become progressively more important. PHASTEST not only offers faster and more accurate prophage annotations than its predecessors, it also provides more complete whole genome annotations and much improved genome visualization capabilities. In standardized tests, we found that PHASTEST is 31% faster and 2-3% more accurate in prophage identification than PHASTER. Specifically, PHASTEST can process a typical bacterial genome in 3.2 min (raw sequence) or in 1.3 min when given a pre-annotated GenBank file. Improvements in PHASTEST's ability to annotate bacterial genomes now make it a particularly powerful tool for whole genome annotation. In addition, PHASTEST now offers a much more modern and responsive visualization interface that allows users to generate, edit, annotate and interactively visualize (via zooming, rotating, dragging, panning, resetting), colourful, publication quality genome maps. PHASTEST continues to offer popular options such as an API for programmatic queries, a Docker image for local installations, support for multiple (metagenomic) queries and the ability to perform automated look-ups against thousands of previously PHAST-annotated bacterial genomes. PHASTEST is available online at https://phastest.ca.
Topics: Databases, Nucleic Acid; Genome, Bacterial; Molecular Sequence Annotation; Plasmids; Prophages; Search Engine; Software
PubMed: 37194694
DOI: 10.1093/nar/gkad382 -
Journal of Bacteriology Aug 2023The operon of Qin cryptic prophage in Escherichia coli K-12 encodes the small RNA (sRNA) DicF and small protein DicB, which regulate host cell division and are toxic...
The operon of Qin cryptic prophage in Escherichia coli K-12 encodes the small RNA (sRNA) DicF and small protein DicB, which regulate host cell division and are toxic when overexpressed. While new functions of DicB and DicF have been identified in recent years, the mechanisms controlling the expression of the operon have remained unclear. Transcription from the major promoter of the operon, is repressed by DicA. In this study, we discovered that transcription of the operon and processing of the polycistronic mRNA is regulated by multiple mechanisms. DicF sRNA accumulates during stationary phase and is processed from the polycistronic mRNA by the action of both RNase III and RNase E. DicA-mediated transcriptional repression of can be relieved by an antirepressor protein, Rem, encoded on the Qin prophage. Ectopic production of Rem results in cell filamentation due to strong induction of the operon, and filamentation is mediated by DicF and DicB. Spontaneous derepression of occurs in a subpopulation of cells independent of the antirepressor. This phenomenon is reminiscent of the bistable switch of λ phage with DicA and DicC performing functions similar to those of CI and Cro, respectively. Additional experiments demonstrate stress-dependent induction of the operon. Collectively, our results illustrate that toxic genes carried on cryptic prophages are subject to layered mechanisms of control, some that are derived from the ancestral phage and some that are likely later adaptations. Cryptic or defective prophages have lost genes necessary to excise from the bacterial chromosome and produce phage progeny. In recent years, studies have found that cryptic prophage gene products influence diverse aspects of bacterial host cell physiology. However, to obtain a complete understanding of the relationship between cryptic prophages and the host bacterium, identification of the environmental, host, or prophage-encoded factors that induce the expression of cryptic prophage genes is crucial. In this study, we examined the regulation of a cryptic prophage operon in Escherichia coli encoding a small RNA and a small protein that are involved in inhibiting bacterial cell division, altering host metabolism, and protecting the host bacterium from phage infections.
Topics: Escherichia coli; Prophages; Escherichia coli K12; Bacteriophage lambda; Bacteria; RNA, Small Untranslated
PubMed: 37439671
DOI: 10.1128/jb.00129-23 -
Molecular Microbiology Nov 2022Compared to bacteria of the gut microbiota, bacteriophages are still poorly characterised, and their physiological importance is far less known. Temperate phages are... (Review)
Review
Compared to bacteria of the gut microbiota, bacteriophages are still poorly characterised, and their physiological importance is far less known. Temperate phages are probably a major actor in the gut, as it is estimated that 80% of intestinal bacteria are lysogens, meaning that they are carrying prophages. In addition, prophage induction rates are higher in the gut than in vitro. However, studies on the signals leading to prophage induction have essentially focused on genotoxic agents with poor relevance for this environment. In this review, we sum up recent findings about signals able to trigger prophage induction in the gut. Three categories of signals are at play: those originating from interactions between intestinal microbes, those from the human or animal host physiology and those from external intakes. These recent results highlight the diversity of factors influencing prophage induction in the gut, and start to unveil ways by which microbiota composition may be modulated.
Topics: Animals; Humans; Gastrointestinal Microbiome; Lysogeny; Virus Activation; Prophages; Bacteriophages
PubMed: 36164818
DOI: 10.1111/mmi.14983 -
MSphere Aug 2023Prophages are bacteriophages integrated into the bacterial host's chromosome. This research aims to analyze and characterize the existing prophages within a collection...
Prophages are bacteriophages integrated into the bacterial host's chromosome. This research aims to analyze and characterize the existing prophages within a collection of 53 strains from intensive care units (ICUs) in Portugal and Spain. A total of 113 prophages were localized in the collection, with 18 of them being present in more than one strain simultaneously. After annotation, five of them were discarded as incomplete, and the 13 remaining prophages were characterized. Of 13, 10 belonged to the siphovirus tail morphology group, 2 to the podovirus tail morphology group, and 1 to the myovirus tail morphology group. All prophages had a length ranging from 20,199 to 63,401 bp and a GC% between 56.2% and 63.6%. The number of open reading frames (ORFs) oscillated between 32 and 88, and in 3/13 prophages, more than 50% of the ORFs had an unknown function. With our findings, we show that prophages are present in the majority of the strains isolated from Portuguese and Spanish critically ill patients, many of them found in more than one circulating strain at the same time and following a similar clonal distribution pattern. Although a great sum of ORFs had an unknown function, number of proteins in relation to viral defense (anti-CRISPR proteins, toxin/antitoxin modules, proteins against restriction-modification systems) as well as to prophage interference into their host's quorum sensing system and regulatory cascades were found. This supports the idea that prophages have an influence in bacterial pathogenesis and anti-phage defense. IMPORTANCE Despite being known for decades, prophages remain understudied when compared to the lytic phages employed in phage therapy. This research aims to shed some light into the nature, composition, and role of prophages found within a set of circulating strains of , with special attention to high-risk clones. Given the fact that prophages can effectively influence bacterial pathogenesis, prophage basic research constitutes a topic of growing interest. Furthermore, the abundance of viral defense and regulatory proteins within prophage genomes detected in this study evidences the importance of characterizing the most frequent prophages in circulating clinical strains and in high-risk clones if phage therapy is to be used.
Topics: Humans; Prophages; Pseudomonas aeruginosa; Genome, Viral; Critical Care; Spain
PubMed: 37366636
DOI: 10.1128/msphere.00128-23