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Nature Nov 2023Many bacteria use CRISPR-Cas systems to combat mobile genetic elements, such as bacteriophages and plasmids. In turn, these invasive elements have evolved anti-CRISPR...
Many bacteria use CRISPR-Cas systems to combat mobile genetic elements, such as bacteriophages and plasmids. In turn, these invasive elements have evolved anti-CRISPR proteins to block host immunity. Here we unveil a distinct type of CRISPR-Cas Inhibition strategy that is based on small non-coding RNA anti-CRISPRs (Racrs). Racrs mimic the repeats found in CRISPR arrays and are encoded in viral genomes as solitary repeat units. We show that a prophage-encoded Racr strongly inhibits the type I-F CRISPR-Cas system by interacting specifically with Cas6f and Cas7f, resulting in the formation of an aberrant Cas subcomplex. We identified Racr candidates for almost all CRISPR-Cas types encoded by a diverse range of viruses and plasmids, often in the genetic context of other anti-CRISPR genes. Functional testing of nine candidates spanning the two CRISPR-Cas classes confirmed their strong immune inhibitory function. Our results demonstrate that molecular mimicry of CRISPR repeats is a widespread anti-CRISPR strategy, which opens the door to potential biotechnological applications.
Topics: Bacteria; Bacteriophages; Biotechnology; CRISPR-Associated Proteins; CRISPR-Cas Systems; Molecular Mimicry; Plasmids; Prophages; RNA, Viral
PubMed: 37853129
DOI: 10.1038/s41586-023-06612-5 -
Microorganisms Sep 2023The review provides an overview of the current status of the solvent-producing clostridia. The origin and development of industrial clostridial species, as well as the... (Review)
Review
The review provides an overview of the current status of the solvent-producing clostridia. The origin and development of industrial clostridial species, as well as the history of the industrial Acetone Butanol Ethanol fermentation process, is reexamined, and the recent resurgence of interest in the production of biobutanol is reviewed. Over 300 fully sequenced genomes for solvent-producing and closely related clostridial species are currently available in public databases. These include 270 genomes sourced from the David Jones culture collection. These genomes were allocated arbitrary DJ codes, and a conversion table to identify the species and strains has now been provided. The expanded genomic database facilitated new comparative genomic and phylogenetic analysis. A synopsis of the common features, molecular taxonomy, and phylogeny of solvent-producing clostridia and the application of comparative phylogenomics are evaluated. A survey and analysis of resident prophages in solvent-producing clostridia are discussed, and the discovery, occurrence, and role of novel R-type tailocins are reported. Prophage genomes with R-type tailocin-like features were detected in all 12 species investigated. The widespread occurrence of tailocins in Gram-negative species is well documented; this survey has indicated that they may also be widespread in clostridia.
PubMed: 37764097
DOI: 10.3390/microorganisms11092253 -
Anaerobe Jun 2024Interactions of bacteria with their viruses named bacteriophages or phages shape the bacterial genome evolution and contribute to the diversity of phages. RNAs have... (Review)
Review
Interactions of bacteria with their viruses named bacteriophages or phages shape the bacterial genome evolution and contribute to the diversity of phages. RNAs have emerged as key components of several anti-phage defense systems in bacteria including CRISPR-Cas, toxin-antitoxin and abortive infection. Frequent association with mobile genetic elements and interplay between different anti-phage defense systems are largely discussed. Newly discovered defense systems such as retrons and CBASS include RNA components. RNAs also perform their well-recognized regulatory roles in crossroad of phage-bacteria regulatory networks. Both regulatory and defensive function can be sometimes attributed to the same RNA molecules including CRISPR RNAs. This review presents the recent advances on the role of RNAs in the bacteria-phage interactions with a particular focus on clostridial species including an important human pathogen, Clostridioides difficile.
Topics: Bacteriophages; Bacteria; RNA, Bacterial; Gene Expression Regulation, Bacterial; CRISPR-Cas Systems; Clostridioides difficile; Humans
PubMed: 38583547
DOI: 10.1016/j.anaerobe.2024.102851 -
Nature Aug 2023Most bacteria in the biosphere are predicted to be polylysogens harbouring multiple prophages. In studied systems, prophage induction from lysogeny to lysis is...
Most bacteria in the biosphere are predicted to be polylysogens harbouring multiple prophages. In studied systems, prophage induction from lysogeny to lysis is near-universally driven by DNA-damaging agents. Thus, how co-residing prophages compete for cell resources if they respond to an identical trigger is unknown. Here we discover regulatory modules that control prophage induction independently of the DNA-damage cue. The modules bear little resemblance at the sequence level but share a regulatory logic by having a transcription factor that activates the expression of a neighbouring gene that encodes a small protein. The small protein inactivates the master repressor of lysis, which leads to induction. Polylysogens that harbour two prophages exposed to DNA damage release mixed populations of phages. Single-cell analyses reveal that this blend is a consequence of discrete subsets of cells producing one, the other or both phages. By contrast, induction through the DNA-damage-independent module results in cells producing only the phage sensitive to that specific cue. Thus, in the polylysogens tested, the stimulus used to induce lysis determines phage productivity. Considering the lack of potent DNA-damaging agents in natural habitats, additional phage-encoded sensory pathways to lysis likely have fundamental roles in phage-host biology and inter-prophage competition.
Topics: Bacteriophages; Lysogeny; Prophages; Viral Proteins; Virus Activation; Bacteria; DNA Damage; DNA, Viral; Single-Cell Analysis; Transcription Factors; Host-Pathogen Interactions
PubMed: 37495698
DOI: 10.1038/s41586-023-06376-y -
Cell Aug 2023Lateral transduction (LT) is the process by which temperate phages mobilize large sections of bacterial genomes. Despite its importance, LT has only been observed during...
Lateral transduction (LT) is the process by which temperate phages mobilize large sections of bacterial genomes. Despite its importance, LT has only been observed during prophage induction. Here, we report that superantigen-carrying staphylococcal pathogenicity islands (SaPIs) employ a related but more versatile and complex mechanism of gene transfer to drive chromosomal hypermobility while self-transferring with additional virulence genes from the host. We found that after phage infection or prophage induction, activated SaPIs form concatamers in the bacterial chromosome by switching between parallel genomic tracks in replication bubbles. This dynamic life cycle enables SaPIbov1 to piggyback its LT of staphylococcal pathogenicity island vSaα, which encodes an array of genes involved in host-pathogen interactions, allowing both islands to be mobilized intact and transferred in a single infective particle. Our findings highlight previously unknown roles of pathogenicity islands in bacterial virulence and show that their evolutionary impact extends beyond the genes they carry.
Topics: Genome, Bacterial; Genomic Islands; Staphylococcus; Virulence; Staphylococcus Phages; Transduction, Genetic
PubMed: 37541198
DOI: 10.1016/j.cell.2023.07.001 -
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 -
Nature Communications Sep 2023Taurine-respiring gut bacteria produce HS with ambivalent impact on host health. We report the isolation and ecophysiological characterization of a taurine-respiring...
Taurine-respiring gut bacteria produce HS with ambivalent impact on host health. We report the isolation and ecophysiological characterization of a taurine-respiring mouse gut bacterium. Taurinivorans muris strain LT0009 represents a new widespread species that differs from the human gut sulfidogen Bilophila wadsworthia in its sulfur metabolism pathways and host distribution. T. muris specializes in taurine respiration in vivo, seemingly unaffected by mouse diet and genotype, but is dependent on other bacteria for release of taurine from bile acids. Colonization of T. muris in gnotobiotic mice increased deconjugation of taurine-conjugated bile acids and transcriptional activity of a sulfur metabolism gene-encoding prophage in other commensals, and slightly decreased the abundance of Salmonella enterica, which showed reduced expression of galactonate catabolism genes. Re-analysis of metagenome data from a previous study further suggested that T. muris can contribute to protection against pathogens by the commensal mouse gut microbiota. Together, we show the realized physiological niche of a key murine gut sulfidogen and its interactions with selected gut microbiota members.
Topics: Humans; Animals; Mice; Affect; Bile Acids and Salts; Salmonella enterica; Taurine; Sulfur
PubMed: 37723166
DOI: 10.1038/s41467-023-41008-z -
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 -
Current Microbiology Jul 2023The genus Liquorilactobacillus is a new genus commonly found in wine and plants. Despite its significance, previous studies on Liquorilactobacillus are primarily focused...
The genus Liquorilactobacillus is a new genus commonly found in wine and plants. Despite its significance, previous studies on Liquorilactobacillus are primarily focused on phenotypic experiments, with limited genome-level studies. This study used comparative genomics to analyze 24 genomes from the genus Liquorilactobacillus, including two novel sequenced strains (IMAU80559 and IMAU80777). A phylogenetic tree of 24 strains was constructed based on 122 core genes and divided into two clades, A and B. Significant differences in GC content were observed between the two clades (P = 10e). Additionally, change revealed to suggests that clade B has more exposure to prophage infection having an upgraded immune system. Further analysis of functional annotation and selective pressure suggests that clade A was subjected to greater selection pressure than B clade (P = 3.9e) and had higher number of functional types annotated than clade B (P = 2.7e), while clade B had a lower number of pseudogenes than clade A (P = 1.9e). The findings suggest that differently prophages and environmental stress may have influenced the common ancestor of clades A and B during evolution, leading to the development of two distinct clades.
Topics: Phylogeny; Genome, Bacterial; Genomics
PubMed: 37420021
DOI: 10.1007/s00284-023-03336-7