Dataset Information

Pneumococcal prophages are diverse, but not without structure or history.

ABSTRACT: Bacteriophages (phages) infect many bacterial species, but little is known about the diversity of phages among the pneumococcus, a leading global pathogen. The objectives of this study were to determine the prevalence, diversity and molecular epidemiology of prophages (phage DNA integrated within the bacterial genome) among pneumococci isolated over the past 90 years. Nearly 500 pneumococcal genomes were investigated and RNA sequencing was used to explore prophage gene expression. We revealed that every pneumococcal genome contained prophage DNA. 286 full-length/putatively full-length pneumococcal prophages were identified, of which 163 have not previously been reported. Full-length prophages clustered into four major groups and every group dated from the 1930-40?s onward. There was limited evidence for genes shared between prophage clusters. Prophages typically integrated in one of five different sites within the pneumococcal genome. 72% of prophages possessed the virulence genes pblA and/or pblB. Individual prophages and the host pneumococcal genetic lineage were strongly associated and some prophages persisted for many decades. RNA sequencing provided clear evidence of prophage gene expression. Overall, pneumococcal prophages were highly prevalent, demonstrated a structured population, possessed genes associated with virulence, and were expressed under experimental conditions. Pneumococcal prophages are likely to play a more important role in pneumococcal biology and evolution than previously recognised.

SUBMITTER: Brueggemann AB

PROVIDER: S-EPMC5317160 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pneumococcal prophages are diverse, but not without structure or history.

Brueggemann Angela B AB Harrold Caroline L CL Rezaei Javan Reza R van Tonder Andries J AJ McDonnell Angus J AJ Edwards Ben A BA

Scientific reports 20170220

Bacteriophages (phages) infect many bacterial species, but little is known about the diversity of phages among the pneumococcus, a leading global pathogen. The objectives of this study were to determine the prevalence, diversity and molecular epidemiology of prophages (phage DNA integrated within the bacterial genome) among pneumococci isolated over the past 90 years. Nearly 500 pneumococcal genomes were investigated and RNA sequencing was used to explore prophage gene expression. We revealed th ...[more]

PMID: 28218261

Similar Datasets

Project description:BackgroundNontuberculous mycobacterial (NTM) infections are increasing in prevalence, with current estimates suggesting that over 100,000 people in the United States are affected each year. It is unclear how certain species of mycobacteria transition from environmental bacteria to clinical pathogens, or what genetic elements influence the differences in virulence among strains of the same species. A potential mechanism of genetic evolution and diversity within mycobacteria is the presence of integrated viruses called prophages in the host genome. Prophages may act as carriers of bacterial genes, with the potential of altering bacterial fitness through horizontal gene transfer. In this study, we quantify the frequency and composition of prophages within mycobacteria isolated from clinical samples and compare them against the composition of PhagesDB, an environmental mycobacteriophage database.MethodsProphages were predicted by agreement between two discovery tools, VirSorter and Phaster, and the frequencies of integrated prophages were compared by growth rate. Prophages were assigned to PhagesDB lettered clusters. Bacterial virulence gene frequency was calculated using a combination of the Virulence Factor Database (VFDB) and the Pathosystems Resource Integration Center virulence database (Patric-VF) within the gene annotation software Prokka. CRISPR elements were discovered using CRT. ARAGORN was used to quantify tRNAs.ResultsRapidly growing mycobacteria (RGM) were more likely to contain prophage than slowly growing mycobacteria (SGM). CRISPR elements were not associated with prophage abundance in mycobacteria. The abundance of tRNAs was enriched in SGM compared to RGM. We compared the abundance of bacterial virulence genes within prophage genomes from clinical isolates to mycobacteriophages from PhagesDB. Our data suggests that prophages from clinical mycobacteria are enriched for bacterial virulence genes relative to environmental mycobacteriophage from PhagesDB.ConclusionProphages are present in clinical NTM isolates. Prophages are more likely to be present in RGM compared to SGM genomes. The mechanism and selective advantage of this enrichment by growth rate remain unclear. In addition, the frequency of bacterial virulence genes in prophages from clinical NTM is enriched relative to the PhagesDB environmental proxy. This suggests prophages may act as a reservoir of genetic elements bacteria could use to thrive within a clinical environment.

Project description:Bacterial genomes commonly carry one or more integrated prophages, although prophage prevalence varies greatly in different bacterial genera and species. We have used the recently developed DEPhT software to discover prophages present in sequenced Mycobacterium genomes. Prophages are unevenly distributed among mycobacteria; Mycobacterium tuberculosis strains are devoid of intact prophages, whereas 75% of Mycobacterium abscessus-chelonae strains carry at least one prophage, and some have up to nine. Newly discovered prophage sequences are generally distinct from those of lytic phages isolated using Mycobacterium smegmatis as a host, although assembly of over 3,800 phage and prophage genomes into clusters based on shared sequence similarity yields seven clusters containing both phage and prophage genomes. M. abscessus prophages use a usually large repertoire of attB sites for prophage integration, and new integration-proficient vectors demonstrate the functionality of integration systems identified in silico and provide tools useful for advancing M. abscessus genetics. Genomic analysis reveals additional accessory and likely mobile parts of Mycobacterium genomes including defective prophages, prophage-like regions, and satellite elements proposed to be candidate phage-inducible chromosomal islands (PICIs). M. abscessus prophages and PICIs are unusual in that they often encode phage-encoded ESX-secreted toxin (PEST) systems that are located adjacent to the phage integration functions and are lysogenically expressed and likely provide a fitness advantage to their host. IMPORTANCE Mycobacterium species include several human pathogens and mycobacteriophages show potential for therapeutic use to control Mycobacterium infections. However, phage infection profiles vary greatly among Mycobacterium abscessus clinical isolates and phage therapies must be personalized for individual patients. Mycobacterium 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 Mycobacterium strains. The prophages are numerous and diverse, especially in M. abscessus 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.

Project description:Trial design: In an earlier trial, Papua New Guinean (PNG) children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3-5 years of age (n = 132), and in 121 community controls of a similar age with no prior pneumococcal vaccination.Methods: Circulating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3-5 years of age for a subgroup of study children.Results: Serotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in all groups had serotype-specific titers ? 0.35?g/ml and ? 1.0 ?g/ml, respectively. Post-challenge antibody titers were higher or similar to pre-challenge titers for most children independent of pneumococcal vaccination history. The rise in antibody titers was significantly lower when pre-challenge titers were higher. Overall the relative number of serotype-specific memory B-cells remained the same or increased between 10 months and 3-5 years of age, and there were no differences in serotype-specific memory B-cell numbers at 3-5 years of age between the three groups.Conclusions: Immunity induced by PCV7 and/or PPV23 immunization in infancy does not exceed that of naturally acquired immunity in 3-5-year-old children living in a highly endemic area. Also, there was no evidence that PPV23 immunization in the first year of life following PCV7 priming induces longer-term hypo-responsiveness.Trial registration: Clinicaltrials.gov NCT01414504 and NCT00219401.

Dataset Information

Pneumococcal prophages are diverse, but not without structure or history.

Publications

Pneumococcal prophages are diverse, but not without structure or history.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets