Comparative Genomics of Cluster O Mycobacteriophages

Cresawn, Steven G.; Pope, Welkin H.; Jacobs-Sera, Deborah; Bowman, Charles A.; Russell, Daniel A.; Dedrick, Rebekah M.; Adair, Tamarah L.; Anders, Kirk R.; Ball, Sarah; Bollivar, David; Breitenberger, Caroline A.; Burnett, Sandra H.; Butela, Kristen; Byrnes, Deanna; Carzo, Sarah; Cornely, Kathleen; Cross, Trevor; Daniels, Richard L.; Dunbar, David; Findley, A. M.; Gissendanner, Chris R.; Golebiewska, Urszula; Hartzog, Grant A.; Hatherill, J. R.; Hughes, Lee E.; Jalloh, Chernoh S.; Santos, Carla De Los; Ekanem, Kevin; Khambule, Sphindile L.; King, Rodney A.; King-Smith, Christina; Klyczek, Karen K.; Krukonis, Greg P.; Laing, Christian; Lapin, Jonathan S.; Lopez, A. Javier; Mkhwanazi, Sipho M.; Molloy, Sally D.; Moran, Deborah; Munsamy, Vanisha; Pacey, Eddie; Plymale, Ruth; Poxleitner, Marianne K.; Reyna, Nathan S.; Schildbach, Joel F.; Stukey, Joseph; Taylor, Sarah E.; Ware, Vassie C.; Wellmann, Amanda; Westholm, Daniel E.; Wodarski, Donna; Zajko, Michelle; Zikalala, Thabiso S.; Hendrix, Roger W.; Hatfull, Graham F.

doi:10.1371/journal.pone.0118725

Cited by 23 publications

(23 citation statements)

References 44 publications

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“…For example, Cluster A phages are similar in size and transcriptional organization, and share an unusual immunity system ( Brown et al, 1997 ; Pope et al, 2011b ). Cluster M phages all contain large numbers of tRNA genes ( Pope et al, 2014a ), Cluster K ( Pope et al, 2011a ) and Cluster O ( Cresawn et al, 2015 ) phages have different but characteristic repeated sequences, and Cluster J phages have an unusual capsid with a triangulation (T) number of 13 ( Pope et al, 2013 ). Therefore, the organization of related mycobacteriophages into clusters provides a framework for identifying and interpreting gene trafficking within and among potentially distinct groups of genomes.…”

Section: Resultsmentioning

confidence: 99%

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

Pope

Bowman

Russell

et al. 2015

eLife

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The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery.DOI: http://dx.doi.org/10.7554/eLife.06416.001

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Section: Resultsmentioning

confidence: 99%

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

Pope

Bowman

Russell

et al. 2015

eLife

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304

331

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“…β-Lactamases were closely inspected, as several reports have suggested their presence on phages (Quiros et al, 2014;Asare et al, 2015a), sometimes with atypical length. Indeed, one such protein annotated as a β-lactamase is, in fact, a tail fiber protein (Cresawn et al, 2015). Half of the putative β-lactamases were rejected because of atypical lengths and/or similarity to tail proteins (see Supplementary Information S4 for the complete analysis of β-lactamase hits, and Supplementary Information S5 for examples of rejected hits).…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, yokD of phage SPβ, encoding a putative aminoglycoside transferase, and three β-lactamases related to those listed in Supplementary Information S4 (gp34 of phage Palmer (99% identical amino acids to phage Pony Gp33), gp62 of mycophage Corndog and gp20 of Mozy (97% identical amino acids to gp20 of phage Che8)) were examined. These last two putative β-lactamases were rejected upon manual inspection, and suspected to be rather phage tail proteins (Cresawn et al, 2015). All four proteins were expressed in Escherichia coli (see Supplementary Information S2 for the origin of genes, and cloning details) and found to be soluble (Supplementary Information S6).…”

Section: Resultsmentioning

confidence: 99%

Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses

Enault¹,

Briet²,

Bouteille³

et al. 2016

The ISME Journal

344

257

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Antibiotic resistance genes (ARGs) are pervasive in gut microbiota, but it remains unclear how often ARGs are transferred, particularly to pathogens. Traditionally, ARG spread is attributed to horizontal transfer mediated either by DNA transformation, bacterial conjugation or generalized transduction. However, recent viral metagenome (virome) analyses suggest that ARGs are frequently carried by phages, which is inconsistent with the traditional view that phage genomes rarely encode ARGs. Here we used exploratory and conservative bioinformatic strategies found in the literature to detect ARGs in phage genomes, and experimentally assessed a subset of ARG predicted using exploratory thresholds. ARG abundances in 1181 phage genomes were vastly overestimated using exploratory thresholds (421 predicted vs 2 known), due to low similarities and matches to protein unrelated to antibiotic resistance. Consistent with this, four ARGs predicted using exploratory thresholds were experimentally evaluated and failed to confer antibiotic resistance in Escherichia coli. Reanalysis of available human- or mouse-associated viromes for ARGs and their genomic context suggested that bona fide ARG attributed to phages in viromes were previously overestimated. These findings provide guidance for documentation of ARG in viromes, and reassert that ARGs are rarely encoded in phages.

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“…Beta-lactamases were also further considered, as genes with homology to beta-lactamases likely play different roles in phages (Asare et al 2015a, Quiros et al 2014, particularly when of atypical length. Indeed, one such protein annotated as a beta-lactamase is in fact a tail fiber protein (Cresawn et al 2015). Half of the putative beta-lactamases were rejected because of atypical lengths and/or similarity to tail proteins (see Supplementary information S4 for the complete analysis of beta-lactamase hits, and Supplementary information S5 for examples of rejected hits).…”

Section: Assessing Informatic Stringencies To Identify Candidate Arg mentioning

confidence: 99%

“…Specifically, yokD of phage SPbeta, encoding a putative aminoglycoside transferase, and three beta-lactamases related to those listed in Supplementary information S4 [gp34 of phage Palmer (99% identical amino-acids to phage Pony Gp33), gp62 of mycophage Corndog and gp20 of Mozy (97% identical amino-acids to gp20 of phage Che8)] were examined. These last two putative beta-lactamases were rejected upon manual inspection, and suspected to be rather phage tail proteins (Cresawn et al 2015). All four proteins were expressed in Escherichia coli (see Supplementary information S2 for the origin of genes, and cloning details) and found to be soluble (Supplementary information S6).…”

Section: Experimental Testing Of Four Putative Phage-encoded Argmentioning

confidence: 99%

Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses

Enault

Briet

Bouteille

et al. 2016

Preprint

View full text Add to dashboard Cite

Antibiotic resistance genes (ARG) are pervasive in gut microbiota, but it remains unclear how often ARG are transferred, particularly to pathogens. Traditionally, ARG spread is attributed to horizontal transfer mediated either by DNA transformation, bacterial conjugation or generalized transduction. However, recent viral metagenome (virome) analyses suggest that ARG are frequently carried by phages, which is inconsistent with the traditional view that phage genomes rarely encode ARG. Here we used exploratory and conservative bioinformatic strategies found in the literature to detect ARG in phage genomes, and experimentally assessed a subset of ARG predicted using exploratory thresholds. ARG abundances in 1,181 phage genomes were vastly over-estimated using exploratory thresholds (421 predicted vs 2 known), due to low similarities and matches to protein unrelated to antibiotic resistance. Consistent with this, 4 ARG predicted using exploratory thresholds were experimentally evaluated and failed to confer antibiotic resistance in Escherichia coli. Re-analysis of available human-or mouse-associated viromes for ARG and their genomic context suggested that bona fide ARG attributed to phages in viromes were previously over-estimated. These findings provide guidance for documentation of ARG in viromes, and re-assert that ARG are rarely encoded in phages.

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Comparative Genomics of Cluster O Mycobacteriophages

Cited by 23 publications

References 44 publications

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses

Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses

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