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Infection, Genetics and Evolution :... Sep 2023To systematically investigate the prophages carrying in Porphyromonas gingivalis (P. gingivalis) strains, analyze potential antibiotic resistance genes (ARGs) and...
To systematically investigate the prophages carrying in Porphyromonas gingivalis (P. gingivalis) strains, analyze potential antibiotic resistance genes (ARGs) and virulence genes in these prophages. We collected 90 whole genome sequences of P. gingivalis from NCBI and utilized the Prophage Hunter online software to predict prophages; Comprehensive antibiotic research database (CARD) and virulence factors database (VFDB) were adopted to analyze the ARGs and virulence factors (VFs) carried by the prophages. Sixty-nine prophages were identified among 24/90 P. gingivalis strains, including 17 active prophages (18.9%) and 52 ambiguous prophages (57.8%). The proportion of prophages carried by each P. gingivalis genome ranged from 0.5% to 6.7%. A total of 188 antibiotic resistance genes belonging to 25 phenotypes and 46 different families with six mechanisms of antibiotic resistance were identified in the 17 active prophages. Three active prophages encoded 4 virulence genes belonging to type III and type VI secretion systems. The potential hosts of these virulence genes included Escherichia coli, Shigella sonnei, Salmonella typhi, and Klebsiella pneumoniae. In conclusion, 26.7% P. gingivalis strains carry prophages, while the proportion of prophage genes in the P. gingivalis genome is relatively low. In addition, approximately 39.7% of the P. gingivalis prophage genes have ARGs identified, mainly against streptogramin, peptides, and aminoglycosides. Only a few prophages carry virulence genes. Prophages may play an important role in the acquisition, dissemination of antibiotic resistance genes, and pathogenicity evolution in P. gingivalis.
Topics: Prophages; Genome, Bacterial; Porphyromonas gingivalis; Virulence Factors; Virulence; Escherichia coli; Anti-Bacterial Agents
PubMed: 37572952
DOI: 10.1016/j.meegid.2023.105489 -
FEMS Microbiology Letters Mar 2016Bacteriophages are viruses that infect bacteria. There are an estimated 10(31) phage on the planet, making them the most abundant form of life. We are rapidly... (Review)
Review
Bacteriophages are viruses that infect bacteria. There are an estimated 10(31) phage on the planet, making them the most abundant form of life. We are rapidly approaching the centenary of their identification, and yet still have only a limited understanding of their role in the ecology and evolution of bacterial populations. Temperate prophage carriage is often associated with increased bacterial virulence. The rise in use of technologies, such as genome sequencing and transcriptomics, has highlighted more subtle ways in which prophages contribute to pathogenicity. This review discusses the current knowledge of the multifaceted effects that phage can exert on their hosts and how this may contribute to bacterial adaptation during infection.
Topics: Bacteria; Bacterial Infections; Bacteriophages; Exotoxins; Life Cycle Stages; Lysogeny; Prophages; Virulence Factors
PubMed: 26825679
DOI: 10.1093/femsle/fnw015 -
Infection, Genetics and Evolution :... Aug 2021Mycoplasma anserisalpingitidis is a bacterial waterfowl pathogen. In these days of growing antibiotic resistance, it is necessary to search for alternative methods of...
Mycoplasma anserisalpingitidis is a bacterial waterfowl pathogen. In these days of growing antibiotic resistance, it is necessary to search for alternative methods of defense against Mycoplasma impacts in flocks. In order to identify prophage-like sequences, three established bioinformatics tools (PHASTER, PhiSpy, Prophage Hunter) were used in this study for the in silico screening of 82 M. anserisalpingitidis whole genomes. The VIBRANT software was used as a novel approach to further investigate the possibility of prophages in the sequences. The commonly used softwares found prophage-like sequences in the strains, but the results were inconclusive. The VIBRANT search resulted in multiple hits, and many of them were over 10,000 base pairs (bp). These putative prophages are comparable in size to the few described mycoplasma phages. The translated coding DNA sequences of the putative prophages were checked with protein BLAST. The functions of the proteins found by the BLASTP search are common among bacteriophages. The BLASTN search of the sequences found that many of these were more similar to the M. anatis NCTC 10156 strain, rather than the available M. anserisalpingitidis strains. The initial screening pointed at the presence of novel bacteriophages in the M. anserisalpingitidis and M. anatis strains. The VIBRANT search results were very similar to each other and none of these sequences were part of the core genome of M. anserisalpingitidis, with a few exceptions. The VIBRANT analysis explored presumably intact, novel prophages.
Topics: Mycoplasma; Prophages
PubMed: 33932611
DOI: 10.1016/j.meegid.2021.104886 -
NPJ Biofilms and Microbiomes Oct 2023Elimination of specific enteropathogenic microorganisms is critical to gut health. However, the complexity of the gut community makes it challenging to target specific...
Elimination of specific enteropathogenic microorganisms is critical to gut health. However, the complexity of the gut community makes it challenging to target specific bacterial organisms. Accumulating evidence suggests that various foods can change the abundance of intestinal bacteria by modulating prophage induction. By using pathogenic Escherichia coli (E. coli) ATCC 25922 as a model in this research, we explored the potential of dietary modulation of prophage induction and subsequent bacterial survival. Among a panel of sugars tested in vitro, D-xylose was shown to efficiently induce prophages in E. coli ATCC 25922, which depends, in part, upon the production of D-lactic acid. In an enteric mouse model, prophage induction was found to be further enhanced in response to propionic acid. Dietary D-xylose increased the proportion of Clostridia which converted D-lactic acid to propionic acid. Intestinal propionic acid levels were diminished, following either oral gavage with the dehydrogenase gene (ldhA)-deficient E. coli ATCC 25922 or depletion of intestinal Clostridia by administration of streptomycin. D-Xylose metabolism and exposure to propionic acid triggered E. coli ATCC 25922 SOS response that promoted prophage induction. E. coli ATCC 25922 mutant of RecA, a key component of SOS system, exhibited decreased phage production. These findings suggest the potential of using dietary components that can induce prophages as antimicrobial alternatives for disease control and prevention by targeted elimination of harmful gut bacteria.
Topics: Mice; Animals; Bacteriophages; Escherichia coli; Xylose; Prophages; Lactic Acid
PubMed: 37821428
DOI: 10.1038/s41522-023-00445-w -
International Journal of Molecular... Jun 2018The review uses the , the gastric bacterium that colonizes the human stomach, to address how to obtain information from bacterial genomes about prophage biology. In a... (Review)
Review
The review uses the , the gastric bacterium that colonizes the human stomach, to address how to obtain information from bacterial genomes about prophage biology. In a time of continuous growing number of genomes available, this review provides tools to explore genomes for prophage presence, or other mobile genetic elements and virulence factors. The review starts by covering the genetic diversity of and then moves to the biologic basis and the bioinformatics approaches used for studding the phage biology from their genomes and how this is related with the bacterial population structure. Aspects concerning prophage biology, evolution and phylogeography are discussed.
Topics: Africa; Asia; Bayes Theorem; Biological Coevolution; Europe; Genes, Essential; Genome, Bacterial; Genome, Viral; Helicobacter Infections; Helicobacter pylori; History, Ancient; Human Migration; Humans; Interspersed Repetitive Sequences; Phylogeny; Phylogeography; Prophages; Virulence Factors; Whole Genome Sequencing
PubMed: 29933614
DOI: 10.3390/ijms19071831 -
Microbiology (Reading, England) Mar 2022subspecies serovar Typhimurium (. Typhimurium) definitive phage type 104 (DT104), . Worthington, and produce ArtAB toxin, which catalyses ADP-ribosylation of...
subspecies serovar Typhimurium (. Typhimurium) definitive phage type 104 (DT104), . Worthington, and produce ArtAB toxin, which catalyses ADP-ribosylation of pertussis toxin-sensitive G protein. ArtAB gene () is encoded on a prophage in , and prophage induction by SOS-inducing agents is associated with increases in ArtAB production . However, little is known about the expression of . Here, we showed a significant increase in transcription of DT104 within macrophage-like RAW264.7 cells. Intracellular expression of ArtAB was also observed by immunofluorescence staining. The induced expression of in DT104 and was enhanced by treatment of RAW264.7 cells with phorbol 12-myristate 13-acetate (PMA), which stimulates the production of reactive oxygen species (ROS); however, such induction was not observed in . Worthington. Upregulation of , a major regulator of oxidative stress, and a repressor of prophage induction, was observed in . Worthington within RAW264.7 cells treated with PMA but not in the DT104 strain. Although the expression of was increased, was upregulated in which lacks the gene in the incomplete -encoded prophage. Taken together, oxidative stress plays a role in the production of toxins in macrophages, and high expression levels of and are responsible for the low expression of . Therefore, strain variation in the level of expression within macrophages could be explained by differences in the oxidative stress response of bacteria and might be reflected in its virulence.
Topics: Macrophages; Prophages; Salmonella typhimurium; Virulence
PubMed: 35333707
DOI: 10.1099/mic.0.001152 -
Virus Research Apr 2023Bacteriophages are viruses that exclusively infect bacteria which require local degradation of cell barriers. This degradation is accomplished by various lysins located...
Bacteriophages are viruses that exclusively infect bacteria which require local degradation of cell barriers. This degradation is accomplished by various lysins located mainly within the phage tail structure. In this paper we surveyed and analysed the genomes of 506 isolated bacteriophage and prophage infecting or harboured within the genomes of the medically important Enterococcus faecalis and faecium. We highlight and characterise the major features of the genomes of phage in the morphological groups podovirus, siphovirus and myovirus, and explore their categorisation according to the new ICTV classifications, with a focus on putative extracellular lysins chiefly within tail modules. Our analysis reveals a range of potential cell-wall targeting enzyme domains that are part of tail, tape measure or other predicted base structures of these phages or prophages. These largely fall into protein domains targeting pentapeptide or glycosidic linkages within peptidoglycan but also potentially the enterococcal polysaccharide antigen (EPA) and wall teichoic acids of these species (i.e., Pectinesterases and Phosphodiesterases). Notably, there is a great variety of domain architectures that reveal the diversity of evolutionary solutions to attack the Enterococcus cell wall. Despite this variety, most phage and prophage possess a putative endopeptidase (70%), reflecting the ubiquity of this cell surface barrier. We also identified a predicted lytic transglycosylase domain belonging to the glycosyl hydrolase (GH) family 23 and present exclusively within tape measure proteins. Our data also reveal distinct features of the genomes of podo-, sipho- and myo-type viruses that most likely relate to their size and complexity. Overall, we lay a foundation for expression of recombinant TAL proteins and engineering of enterococcal and other phage that will be invaluable for researchers in this field.
Topics: Bacteriophages; Prophages; Biological Evolution; Bacteria; Enterococcus
PubMed: 36787848
DOI: 10.1016/j.virusres.2023.199073 -
Microbiome Jul 2023Porphyromonas gingivalis (hereafter "Pg") is an oral pathogen that has been hypothesized to act as a keystone driver of inflammation and periodontal disease. Although Pg...
BACKGROUND
Porphyromonas gingivalis (hereafter "Pg") is an oral pathogen that has been hypothesized to act as a keystone driver of inflammation and periodontal disease. Although Pg is most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized by Pg. Insights into the factors shaping the striking strain-level variation in Pg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. One of the key forces often shaping strain-level diversity in microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, although Pg has been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg.
RESULTS
Here we systematically addressed the question of whether Pg are infected by phages-and we found that they are. We found that prophages are common in Pg, they are genomically diverse, and they encode genes that have the potential to alter Pg physiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems in Pg, and that Pg strains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain-level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a model Pg strain are active in culture, producing extracellular viral particles in broth cultures.
CONCLUSION
This work definitively establishes that phages are a major unrecognized force shaping the ecology and intra-species strain-level diversity of the well-studied oral pathogen Pg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known about Pg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly. Video Abstract.
Topics: Humans; Bacteriophages; Porphyromonas gingivalis; Prophages; Periodontal Diseases; Base Sequence
PubMed: 37491415
DOI: 10.1186/s40168-023-01607-w -
MBio Feb 2024Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems...
Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by the (repressor), , , and genes. Here we report that the P22-encoded SieA protein is necessary and sufficient for exclusion by the SieA system and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three "ejection proteins" after their release from the virion. Phage P22 mutants that overcome the SieA block were isolated, and they have amino acid changes in the C-terminal regions of the gene and encoded ejection proteins. Three different single-amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in phage target specificity. Our data strongly suggest a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.IMPORTANCEThe ongoing evolutionary battle between bacteria and the viruses that infect them is a critical feature of bacterial ecology on Earth. Viruses can kill bacteria by infecting them. However, when their chromosomes are integrated into a bacterial genome as a prophage, viruses can also protect the host bacterium by expressing genes whose products defend against infection by other viruses. This defense property is called "superinfection exclusion." A significant fraction of bacteria harbor prophages that encode such protective systems, and there are many different molecular strategies by which superinfection exclusion is mediated. This report is the first to describe the mechanism by which bacteriophage P22 SieA superinfection exclusion protein protects its host bacterium from infection by other P22-like phages. The P22 prophage-encoded inner membrane SieA protein prevents infection by blocking transport of superinfecting phage DNA across the inner membrane during injection.
Topics: Humans; Bacteriophage P22; Superinfection; Bacteriophages; Prophages; Membrane Proteins; DNA; Amino Acids
PubMed: 38236051
DOI: 10.1128/mbio.02169-23 -
Frontiers in Cellular and Infection... 2023is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The QS...
is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The QS system of is responsible for the biosynthesis of diverse 2-alkyl-4-quinolones (AQs), of which 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4()-quinolone (PQS) function as QS signal molecules. Transcriptomic analyses revealed that HHQ and PQS influenced the expression of multiple genes via PqsR-dependent and -independent pathways whereas 2-heptyl-4-hydroxyquinoline -oxide (HQNO) had no effect on transcriptome. HQNO is a cytochrome inhibitor that causes programmed cell death and autolysis. However, mutants unable to synthesize HQNO undergo autolysis when grown as colony biofilms. The mechanism by which such autolysis occurs is not understood. Through the generation and phenotypic characterization of multiple PAO1 mutants producing altered levels of AQs in different combinations, we demonstrate that mutation of results in the accumulation of HHQ which in turn leads to Pf4 prophage activation and consequently autolysis. Notably, the effect of HHQ on Pf4 activation is not mediated its cognate receptor PqsR. These data indicate that the synthesis of HQNO in PAO1 limits HHQ-induced autolysis mediated by Pf4 in colony biofilms. A similar phenomenon is shown to occur in cystic fibrosis (CF) isolates, in which the autolytic phenotype can be abrogated by ectopic expression of .
Topics: Humans; Quinolones; Quorum Sensing; Pseudomonas aeruginosa; Prophages; Biofilms; Autolysis
PubMed: 37305419
DOI: 10.3389/fcimb.2023.1183681