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Article ; Online: Unusual prophages in Mycobacterium abscessus genomes and strain variations in phage susceptibilities.

Elizabeth D Amarh / Rebekah M Dedrick / Rebecca A Garlena / Daniel A Russell / Christian H Gauthier / Haley G Aull / Lawrence Abad / Deborah Jacobs-Sera / Chidiebere Akusobi / Eric J Rubin / Graham F Hatfull

PLoS ONE, Vol 18, Iss 2, p e

2023 Volume 0281769

Abstract: Mycobacterium abscessus infections are relatively common in patients with cystic fibrosis and are clinically challenging, with frequent intrinsic resistance to antibiotics. Therapeutic treatment with bacteriophages offers some promise but faces many ... ...

Abstract	Mycobacterium abscessus infections are relatively common in patients with cystic fibrosis and are clinically challenging, with frequent intrinsic resistance to antibiotics. Therapeutic treatment with bacteriophages offers some promise but faces many challenges including substantial variation in phage susceptibilities among clinical isolates, and the need to personalize therapies for individual patients. Many strains are not susceptible to any phages or are not efficiently killed by lytic phages, including all smooth colony morphotype strains tested to-date. Here, we analyze a set of new M. abscessus isolates for the genomic relationships, prophage content, spontaneous phage release, and phage susceptibilities. We find that prophages are common in these M. abscessus genomes, but some have unusual arrangements, including tandemly integrated prophages, internal duplications, and they participate in active exchange of polymorphic toxin-immunity cassettes secreted by ESX systems. Relatively few strains are efficiently infected by any mycobacteriophages, and the infection patterns do not reflect the overall phylogenetic relationships of the strains. Characterization of these strains and their phage susceptibility profiles will help to advance the broader application of phage therapies for NTM infections.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic diversity of bacteriophages infecting Rhodobacter capsulatus and their relatedness to its gene transfer agent RcGTA.

Jackson Rapala / Brenda Miller / Maximiliano Garcia / Megan Dolan / Matthew Bockman / Mats Hansson / Daniel A Russell / Rebecca A Garlena / Steven G Cresawn / Alexander B Westbye / J Thomas Beatty / Richard M Alvey / David W Bollivar

PLoS ONE, Vol 16, Iss 11, p e

2021 Volume 0255262

Abstract: The diversity of bacteriophages is likely unparalleled in the biome due to the immense variety of hosts and the multitude of viruses that infect them. Recent efforts have led to description at the genomic level of numerous bacteriophages that infect the ... ...

Abstract	The diversity of bacteriophages is likely unparalleled in the biome due to the immense variety of hosts and the multitude of viruses that infect them. Recent efforts have led to description at the genomic level of numerous bacteriophages that infect the Actinobacteria, but relatively little is known about those infecting other prokaryotic phyla, such as the purple non-sulfur photosynthetic α-proteobacterium Rhodobacter capsulatus. This species is a common inhabitant of freshwater ecosystems and has been an important model system for the study of photosynthesis. Additionally, it is notable for its utilization of a unique form of horizontal gene transfer via a bacteriophage-like element known as the gene transfer agent (RcGTA). Only three bacteriophages of R. capsulatus had been sequenced prior to this report. Isolation and characterization at the genomic level of 26 new bacteriophages infecting this host advances the understanding of bacteriophage diversity and the origins of RcGTA. These newly discovered isolates can be grouped along with three that were previously sequenced to form six clusters with four remaining as single representatives. These bacteriophages share genes with RcGTA that seem to be related to host recognition. One isolate was found to cause lysis of a marine bacterium when exposed to high-titer lysate. Although some clusters are more highly represented in the sequenced genomes, it is evident that many more bacteriophage types that infect R. capsulatus are likely to be found in the future.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic diversity of bacteriophages infecting Rhodobacter capsulatus and their relatedness to its gene transfer agent RcGTA

Jackson Rapala / Brenda Miller / Maximiliano Garcia / Megan Dolan / Matthew Bockman / Mats Hansson / Daniel A. Russell / Rebecca A. Garlena / Steven G. Cresawn / Alexander B. Westbye / J. Thomas Beatty / Richard M. Alvey / David W. Bollivar

PLoS ONE, Vol 16, Iss

2021 Volume 11

Abstract	The diversity of bacteriophages is likely unparalleled in the biome due to the immense variety of hosts and the multitude of viruses that infect them. Recent efforts have led to description at the genomic level of numerous bacteriophages that infect the Actinobacteria, but relatively little is known about those infecting other prokaryotic phyla, such as the purple non-sulfur photosynthetic α-proteobacterium Rhodobacter capsulatus. This species is a common inhabitant of freshwater ecosystems and has been an important model system for the study of photosynthesis. Additionally, it is notable for its utilization of a unique form of horizontal gene transfer via a bacteriophage-like element known as the gene transfer agent (RcGTA). Only three bacteriophages of R. capsulatus had been sequenced prior to this report. Isolation and characterization at the genomic level of 26 new bacteriophages infecting this host advances the understanding of bacteriophage diversity and the origins of RcGTA. These newly discovered isolates can be grouped along with three that were previously sequenced to form six clusters with four remaining as single representatives. These bacteriophages share genes with RcGTA that seem to be related to host recognition. One isolate was found to cause lysis of a marine bacterium when exposed to high-titer lysate. Although some clusters are more highly represented in the sequenced genomes, it is evident that many more bacteriophage types that infect R. capsulatus are likely to be found in the future.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

Welkin H Pope / Charles A Bowman / Daniel A Russell / Deborah Jacobs-Sera / David J Asai / Steven G Cresawn / William R Jacobs Jr / Roger W Hendrix / Jeffrey G Lawrence / Graham F Hatfull / Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science / Phage Hunters Integrating Research and Education / Mycobacterial Genetics Course

eLife, Vol

2015 Volume 4

Abstract: 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 ... ...

Abstract	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.
Keywords	bacteriophage ; genomic ; evolution ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2015-04-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic diversity of bacteriophages infecting Microbacterium spp.

Deborah Jacobs-Sera / Lawrence A Abad / Richard M Alvey / Kirk R Anders / Haley G Aull / Suparna S Bhalla / Lawrence S Blumer / David W Bollivar / J Alfred Bonilla / Kristen A Butela / Roy J Coomans / Steven G Cresawn / Tom D'Elia / Arturo Diaz / Ashley M Divens / Nicholas P Edgington / Gregory D Frederick / Maria D Gainey / Rebecca A Garlena /

Kenneth W Grant / Susan M R Gurney / Heather L Hendrickson / Lee E Hughes / Margaret A Kenna / Karen K Klyczek / Hari Kotturi / Travis N Mavrich / Angela L McKinney / Evan C Merkhofer / Jordan Moberg Parker / Sally D Molloy / Denise L Monti / Dana A Pape-Zambito / Richard S Pollenz / Welkin H Pope / Nathan S Reyna / Claire A Rinehart / Daniel A Russell / Christopher D Shaffer / Viknesh Sivanathan / Ty H Stoner / Joseph Stukey / C Nicole Sunnen / Sara S Tolsma / Philippos K Tsourkas / Jamie R Wallen / Vassie C Ware / Marcie H Warner / Jacqueline M Washington / Kristi M Westover

PLoS ONE, Vol 15, Iss 6, p e

2020 Volume 0234636

Abstract: The bacteriophage population is vast, dynamic, old, and genetically diverse. The genomics of phages that infect bacterial hosts in the phylum Actinobacteria show them to not only be diverse but also pervasively mosaic, and replete with genes of unknown ... ...

Abstract	The bacteriophage population is vast, dynamic, old, and genetically diverse. The genomics of phages that infect bacterial hosts in the phylum Actinobacteria show them to not only be diverse but also pervasively mosaic, and replete with genes of unknown function. To further explore this broad group of bacteriophages, we describe here the isolation and genomic characterization of 116 phages that infect Microbacterium spp. Most of the phages are lytic, and can be grouped into twelve clusters according to their overall relatedness; seven of the phages are singletons with no close relatives. Genome sizes vary from 17.3 kbp to 97.7 kbp, and their G+C% content ranges from 51.4% to 71.4%, compared to ~67% for their Microbacterium hosts. The phages were isolated on five different Microbacterium species, but typically do not efficiently infect strains beyond the one on which they were isolated. These Microbacterium phages contain many novel features, including very large viral genes (13.5 kbp) and unusual fusions of structural proteins, including a fusion of VIP2 toxin and a MuF-like protein into a single gene. These phages and their genetic components such as integration systems, recombineering tools, and phage-mediated delivery systems, will be useful resources for advancing Microbacterium genetics.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cluster J mycobacteriophages

Welkin H Pope / Deborah Jacobs-Sera / Aaron A Best / Gregory W Broussard / Pamela L Connerly / Rebekah M Dedrick / Timothy A Kremer / Susan Offner / Amenawon H Ogiefo / Marie C Pizzorno / Kate Rockenbach / Daniel A Russell / Emily L Stowe / Joseph Stukey / Sarah A Thibault / James F Conway / Roger W Hendrix / Graham F Hatfull

PLoS ONE, Vol 8, Iss 7, p e

intron splicing in capsid and tail genes.

2013 Volume 69273

Abstract: Bacteriophages isolated on Mycobacterium smegmatis mc(2)155 represent many distinct genomes sharing little or no DNA sequence similarity. The genomes are architecturally mosaic and are replete with genes of unknown function. A new group of genomes ... ...

Abstract	Bacteriophages isolated on Mycobacterium smegmatis mc(2)155 represent many distinct genomes sharing little or no DNA sequence similarity. The genomes are architecturally mosaic and are replete with genes of unknown function. A new group of genomes sharing substantial nucleotide sequences constitute Cluster J. The six mycobacteriophages forming Cluster J are morphologically members of the Siphoviridae, but have unusually long genomes ranging from 106.3 to 117 kbp. Reconstruction of the capsid by cryo-electron microscopy of mycobacteriophage BAKA reveals an icosahedral structure with a triangulation number of 13. All six phages are temperate and homoimmune, and prophage establishment involves integration into a tRNA-Leu gene not previously identified as a mycobacterial attB site for phage integration. The Cluster J genomes provide two examples of intron splicing within the virion structural genes, one in a major capsid subunit gene, and one in a tail gene. These genomes also contain numerous free-standing HNH homing endonuclease, and comparative analysis reveals how these could contribute to genome mosaicism. The unusual Cluster J genomes provide new insights into phage genome architecture, gene function, capsid structure, gene mobility, intron splicing, and evolution.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative genomics of Cluster O mycobacteriophages.

Steven G Cresawn / Welkin H Pope / Deborah Jacobs-Sera / Charles A Bowman / Daniel A Russell / Rebekah M Dedrick / Tamarah Adair / Kirk R Anders / Sarah Ball / David Bollivar / Caroline Breitenberger / Sandra H Burnett / Kristen Butela / Deanna Byrnes / Sarah Carzo / Kathleen A Cornely / Trevor Cross / Richard L Daniels / David Dunbar /

Ann M Findley / Chris R Gissendanner / Urszula P Golebiewska / Grant A Hartzog / J Robert Hatherill / Lee E Hughes / Chernoh S Jalloh / Carla De Los Santos / Kevin Ekanem / Sphindile L Khambule / Rodney A King / Christina King-Smith / Karen Klyczek / Greg P Krukonis / Christian Laing / Jonathan S Lapin / A Javier Lopez / Sipho M Mkhwanazi / Sally D Molloy / Deborah Moran / Vanisha Munsamy / Eddie Pacey / Ruth Plymale / Marianne Poxleitner / Nathan Reyna / Joel F Schildbach / Joseph Stukey / Sarah E Taylor / Vassie C Ware / Amanda L Wellmann / Daniel Westholm

PLoS ONE, Vol 10, Iss 3, p e

2015 Volume 0118725

Abstract: Mycobacteriophages--viruses of mycobacterial hosts--are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages--Corndog, ... ...

Abstract	Mycobacteriophages--viruses of mycobacterial hosts--are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages--Corndog, Catdawg, Dylan, Firecracker, and YungJamal--designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cluster K mycobacteriophages

Welkin H Pope / Christina M Ferreira / Deborah Jacobs-Sera / Robert C Benjamin / Ariangela J Davis / Randall J DeJong / Sarah C R Elgin / Forrest R Guilfoile / Mark H Forsyth / Alexander D Harris / Samuel E Harvey / Lee E Hughes / Peter M Hynes / Arrykka S Jackson / Marilyn D Jalal / Elizabeth A MacMurray / Coreen M Manley / Molly J McDonough / Jordan L Mosier /

PLoS ONE, Vol 6, Iss 10, p e

insights into the evolutionary origins of mycobacteriophage TM4.

2011 Volume 26750

Abstract: Five newly isolated mycobacteriophages--Angelica, CrimD, Adephagia, Anaya, and Pixie--have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence ... ...

Abstract	Five newly isolated mycobacteriophages--Angelica, CrimD, Adephagia, Anaya, and Pixie--have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them--with the exception of TM4--form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Expanding the diversity of mycobacteriophages

Welkin H Pope / Deborah Jacobs-Sera / Daniel A Russell / Craig L Peebles / Zein Al-Atrache / Turi A Alcoser / Lisa M Alexander / Matthew B Alfano / Samantha T Alford / Nichols E Amy / Marie D Anderson / Alexander G Anderson / Andrew A S Ang / Manuel Ares / Amanda J Barber / Lucia P Barker / Jonathan M Barrett / William D Barshop / Cynthia M Bauerle /

Ian M Bayles / Katherine L Belfield / Aaron A Best / Agustin Borjon / Charles A Bowman / Christine A Boyer / Kevin W Bradley / Victoria A Bradley / Lauren N Broadway / Keshav Budwal / Kayla N Busby / Ian W Campbell / Anne M Campbell / Alyssa Carey / Steven M Caruso / Rebekah D Chew / Chelsea L Cockburn / Lianne B Cohen / Jeffrey M Corajod / Steven G Cresawn / Kimberly R Davis / Lisa Deng / Dee R Denver / Breyon R Dixon / Sahrish Ekram / Sarah C R Elgin / Angela E Engelsen / Belle E V English / Marcella L Erb / Crystal Estrada / Laura Z Filliger

PLoS ONE, Vol 6, Iss 1, p e

insights into genome architecture and evolution.

2011 Volume 16329

Abstract: Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. ... ...

Abstract	Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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