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1.  Mutational Analysis of the Mycobacteriophage BPs Promoter PR Reveals Context-Dependent Sequences for Mycobacterial Gene Expression 
Journal of Bacteriology  2014;196(20):3589-3597.
The PR promoter of mycobacteriophage BPs directs early lytic gene expression and is under the control of the BPs repressor, gp33. Reporter gene fusions showed that PR has modest activity in an extrachromosomal context but has activity that is barely detectable in an integrated context, even in the absence of its repressor. Mutational dissection of PR showed that it uses a canonical −10 hexamer recognized by SigA, and mutants with mutations to the sequence 5′-TATAMT had the greatest activities. It does not contain a 5′-TGN-extended −10 sequence, although mutants with mutations creating an extended −10 sequence had substantially increased promoter activity. Mutations in the −35 hexamer also influenced promoter activity but were strongly context dependent, and similar substitutions in the −35 hexamer differentially affected promoter activity, depending on the −10 and extended −10 motifs. This warrants caution in the construction of synthetic promoters or the bioinformatic prediction of promoter activity. Combinations of mutations throughout PR generated a calibrated series of promoters for expression of stably integrated recombinant genes in both Mycobacterium smegmatis and M. tuberculosis, with maximal promoter activity being more than 2-fold that of the strong hsp60 promoter.
PMCID: PMC4187689  PMID: 25092027
2.  Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood 
mBio  2014;5(6):e02145-14.
Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc2155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.
The mycobacteriophage Patience genome has a notably lower GC content (50.3%) than its Mycobacterium smegmatis host (67.4%) and has markedly different codon usage biases. The viral genome has an abundance of codons that are rare in the host and are decoded by wobble tRNA pairing, although the phage grows well and expression of most of the genes is detected by mass spectrometry. Patience thus has the genomic profile of a virus that evolved primarily in one type of host genetic landscape (moderate-GC bacteria) but has found its way into a distinctly different high-GC environment. Although Patience genes are ill matched to the host expression apparatus, this is of little functional consequence and has not evidently imposed a barrier to migration across the microbial landscape. Interestingly, comparison of expression levels and codon usage profiles reveals evidence of codon selection as the genome evolves and adapts to its new environment.
PMCID: PMC4324244  PMID: 25467442
3.  Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotypes 
Journal of Virology  2014;88(5):2461-2480.
Genomic analysis of a large set of phages infecting the common host Mycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode.
IMPORTANCE The bacteriophage population is vast, dynamic, and old and plays a central role in bacterial pathogenicity. We know surprisingly little about the genetic diversity of the phage population, although metagenomic and phage genome sequencing indicates that it is great. Probing the depth of genetic diversity of phages of a common host, Mycobacterium smegmatis, provides a higher resolution of the phage population and how it has evolved. Three new phages constituting a new cluster M further expand the diversity of the mycobacteriophages and introduce novel features. As such, they provide insights into phage genome architecture, virion structure, and gene regulation at the transcriptional and translational levels.
PMCID: PMC3958112  PMID: 24335314
4.  Genome Sequence of Salmonella enterica subsp. enterica Strain Durban 
Genome Announcements  2014;2(3):e00399-14.
We report the genome sequence of Salmonella enterica subsp. enterica strain Durban, isolated from a patient with salmonellosis and typhoid fever. The strain is closely related to S. enterica subsp. enterica strain P125109 but differs in loss of the ϕSE20 prophage and acquisition of a prophage similar to ELPhiS.
PMCID: PMC4014692  PMID: 24812224
5.  Mycobacteriophages: Windows into Tuberculosis 
PLoS Pathogens  2014;10(3):e1003953.
PMCID: PMC3961340  PMID: 24651299
6.  Generation of Affinity-Tagged Fluoromycobacteriophages by Mixed Assembly of Phage Capsids 
Applied and Environmental Microbiology  2013;79(18):5608-5615.
Addition of affinity tags to bacteriophage particles facilitates a variety of applications, including vaccine construction and diagnosis of bacterial infections. Addition of tags to phage capsids is desirable, as modification of the tails can lead to poor adsorption and loss of infectivity. Although tags can readily be included as fusions to head decoration proteins, many phages do not have decoration proteins as virion components. The addition of a small (10-amino-acid) Strep-tag II (STAG II) to the mycobacteriophage TM4 capsid subunit, gp9, was not tolerated as a genetically homogenous recombinant phage but could be incorporated into the head by growth of wild-type phage on a host expressing the capsid-STAG fusion. Particles with capsids composed of wild-type and STAG-tagged subunit mixtures could be grown to high titers, showed good infectivities, and could be used to isolate phage-bacterium complexes. Preparation of a STAG-labeled fluoromycobacteriophage enabled capture of bacterial complexes and identification of infected bacteria by fluorescence.
PMCID: PMC3754161  PMID: 23851082
7.  A Broadly Implementable Research Course in Phage Discovery and Genomics for First-Year Undergraduate Students 
mBio  2014;5(1):e01051-13.
Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students’ interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training.
Engagement of undergraduate students in scientific research at early stages in their careers presents an opportunity to excite students about science, technology, engineering, and mathematics (STEM) disciplines and promote continued interests in these areas. Many excellent course-based undergraduate research experiences have been developed, but scaling these to a broader impact with larger numbers of students is challenging. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunting Advancing Genomics and Evolutionary Science (SEA-PHAGES) program takes advantage of the huge size and diversity of the bacteriophage population to engage students in discovery of new viruses, genome annotation, and comparative genomics, with strong impacts on bacteriophage research, increased persistence in STEM fields, and student self-identification with learning gains, motivation, attitude, and career aspirations.
PMCID: PMC3950523  PMID: 24496795
8.  Complete Genome Sequences of 63 Mycobacteriophages 
Genome Announcements  2013;1(6):e00847-13.
Mycobacteriophages are viruses that infect mycobacterial hosts. The current collection of sequenced mycobacteriophages—all isolated on a single host strain, Mycobacterium smegmatis mc2155, reveals substantial genetic diversity. The complete genome sequences of 63 newly isolated mycobacteriophages expand the resolution of our understanding of phage diversity.
PMCID: PMC3869317  PMID: 24285655
9.  Evolution of genetic switch complexity 
Bacteriophage  2013;3(1):e24186.
The circuitry of the phage λ genetic switch determining the outcome of lytic or lysogenic growth is well-integrated and complex, raising the question as to how it evolved. It is plausible that it arose from a simpler ancestral switch with fewer components that underwent various additions and refinements, as it adapted to vast numbers of different hosts and conditions. We have recently identified a new class of genetic switches found in mycobacteriophages and other prophages, in which immunity is dependent on integration. These switches contain only three genes (integrase, repressor and cro) and represent a major departure from the λ-like circuitry, lacking many features such as xis, cII and cIII. These small self-contained switches represent an unrealized, elegant circuitry for controlling infection outcome. In this addendum, we propose a model of possible events in the evolution of a complex λ-like switch from a simpler integration-dependent switch.
PMCID: PMC3694055  PMID: 23819104
genetic switch; genetic circuits; bistable; integration-dependent immunity; lytic and lysogenic growth
10.  Mycobacteriophage Marvin: a New Singleton Phage with an Unusual Genome Organization 
Journal of Virology  2012;86(9):4762-4775.
Mycobacteriophages represent a genetically diverse group of viruses that infect mycobacterial hosts. Although more than 80 genomes have been sequenced, these still poorly represent the likely diversity of the broader population of phages that can infect the host, Mycobacterium smegmatis mc2155. We describe here a newly discovered phage, Marvin, which is a singleton phage, having no previously identified close relatives. The 65,100-bp genome contains 107 predicted protein-coding genes arranged in a noncanonical genomic architecture in which a subset of the minor tail protein genes are displaced about 20 kbp from their typical location, situated among nonstructural genes anticipated to be expressed early in lytic growth. Marvin is not temperate, and stable lysogens cannot be recovered from infections, although the presence of a putative xis gene suggests that Marvin could be a relatively recent derivative of a temperate parent. The Marvin genome is replete with novel genes not present in other mycobacteriophage genomes, and although most are of unknown function, the presence of amidoligase and glutamine amidotransferase genes suggests intriguing possibilities for the interactions of Marvin with its mycobacterial hosts.
PMCID: PMC3347389  PMID: 22357284
11.  Propionibacterium acnes Bacteriophages Display Limited Genetic Diversity and Broad Killing Activity against Bacterial Skin Isolates 
mBio  2012;3(5):e00279-12.
Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.
Propionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information for this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.
PMCID: PMC3448167  PMID: 23015740
12.  Complete Genome Sequences of 138 Mycobacteriophages 
Journal of Virology  2012;86(4):2382-2384.
Bacteriophages are the most numerous biological entities in the biosphere, and although their genetic diversity is high, it remains ill defined. Mycobacteriophages—the viruses of mycobacterial hosts—provide insights into this diversity as well as tools for manipulating Mycobacterium tuberculosis. We report here the complete genome sequences of 138 new mycobacteriophages, which—together with the 83 mycobacteriophages previously reported—represent the largest collection of phages known to infect a single common host, Mycobacterium smegmatis mc2 155.
PMCID: PMC3302410  PMID: 22282335
13.  Genome Sequences of Mycobacteriophages AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo, New Members of Cluster B 
Genome Announcements  2015;3(3):e00586-15.
AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo are newly isolated phages of Mycobacterium smegmatis mc2155 discovered in Pittsburgh, Pennsylvania, USA. All five phages share nucleotide similarity with cluster B mycobacteriophages but span considerable diversity with Corofin and OrangeOswald in subcluster B3, AlanGrant and Vincenzo in subcluster B4, and Baee in subcluster B5.
PMCID: PMC4472886  PMID: 26089409
14.  Genome Sequences of Cluster G Mycobacteriophages Cambiare, FlagStaff, and MOOREtheMARYer 
Genome Announcements  2015;3(3):e00595-15.
Mycobacteriophages Cambiare, FlagStaff, and MOOREtheMARYer are newly isolated phages of Mycobacterium smegmatis mc2 155 recovered from soil samples in Pittsburgh, PA. All three genomes are closely related to cluster G mycobacteriophages but differ sufficiently in nucleotide sequence and gene content to warrant division of cluster G into several subclusters.
PMCID: PMC4472887  PMID: 26089410
15.  Genome Sequence of Mycobacteriophage Mindy 
Genome Announcements  2015;3(3):e00596-15.
Mycobacteriophage Mindy is a newly isolated phage of Mycobacterium smegmatis, recovered from a soil sample in Pittsburgh, Pennsylvania, USA. Mindy has a genome length of 75,796 bp, encodes 147 predicted proteins and two tRNAs, and is closely related to mycobacteriophages in cluster E.
PMCID: PMC4472888  PMID: 26089411
16.  Genome Sequence of a Newly Isolated Mycobacteriophage, ShedlockHolmes 
Genome Announcements  2015;3(3):e00597-15.
Mycobacteriophage ShedlockHolmes is a newly isolated phage infecting Mycobacterium smegmatis mc2155. It has a 61,081-bp genome containing 99 predicted protein-coding genes and one tRNA gene. ShedlockHolmes is closely related to mycobacteriophages Pixie, Keshu, and MacnCheese and is a new member of subcluster K3.
PMCID: PMC4472889  PMID: 26089412
17.  Genome Sequence of Mycobacteriophage Phayonce 
Genome Announcements  2015;3(3):e00598-15.
Mycobacteriophage Phayonce is a newly isolated phage recovered from a soil sample in Pittsburgh, PA, using Mycobacterium smegmatis mc2155 as a host. Phayonce’s genome is 49,203 bp long and contains 77 protein-coding genes, 23 of them having predicted functions. Phayonce shares a strong similarity in nucleotide sequence with phages of cluster P.
PMCID: PMC4472890  PMID: 26089413
18.  Genome Sequences of Mycobacteriophages Luchador and Nerujay 
Genome Announcements  2015;3(3):e00599-15.
Luchador and Nerujay are two newly isolated mycobacteriophages recovered from soil samples using Mycobacterium smegmatis. Their genomes are 53,387 bp and 53,455 bp long and have 96 and 97 predicted open reading frames, respectively. Nerujay is related to subcluster A1 phages, and Luchador represents a new subcluster, A14.
PMCID: PMC4472891  PMID: 26089414
19.  Genome Sequence of Mycobacteriophage Momo 
Genome Announcements  2015;3(3):e00601-15.
Momo is a newly discovered phage of Mycobacterium smegmatis mc2155. Momo has a double-stranded DNA genome 154,553 bp in length, with 233 predicted protein-encoding genes, 34 tRNA genes, and one transfer-messenger RNA (tmRNA) gene. Momo has a myoviral morphology and shares extensive nucleotide sequence similarity with subcluster C1 mycobacteriophages.
PMCID: PMC4472892  PMID: 26089415
20.  Genome Sequence of Salmonella enterica Phage Det7 
Genome Announcements  2015;3(3):e00279-15.
Det7 is a Myoviridae bacteriophage that gains entry into its Salmonella enterica serovar Typhimurium host cells by adsorbing to O-antigen polysaccharide. We report here the complete 157,498-bp sequence of its genome. Det7, together with its Vi01-like relatives, are distantly related to phage T4.
PMCID: PMC4424284  PMID: 25953168
21.  Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity 
eLife  null;4:e06416.
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.
eLife digest
Viruses are unable to replicate independently. To generate copies of itself, a virus must instead invade a target cell and commandeer that cell's replication machinery. Different viruses are able to invade different types of cell, and a group of viruses known as bacteriophages (or phages for short) replicate within bacteria. The enormous number and diversity of phages in the world means that they play an important role in virtually every ecosystem.
Despite their importance, relatively little is known about how different phage populations are related to each other and how they evolved. Many phages contain their genetic information in the form of strands of DNA. Using genetic sequencing to find out where and how different genes are encoded in the DNA can reveal information about how different viruses are related to each other. These relationships are particularly complicated in phages, as they can exchange genes with other viruses and microbes.
Previous studies comparing the genomes—the complete DNA sequence—of reasonably small numbers of phages that infect the Mycobacterium group of bacteria have found that the phages can be sorted into ‘clusters’ based on similarities in their genes and where these are encoded in their DNA. However, the number of phages investigated so far has been too small to conclude how different clusters are related. Are the clusters separate, or do they form a ‘continuum’ with different genes and DNA sequences shared between different clusters?
Here, Pope, Bowman, Russell et al. compare the individual genomes of 627 bacteriophages that infect the bacterial species Mycobacterium smegmatis. This is by far the largest number of phage genomes analyzed from a single host species. The large number of genomes analyzed allowed a much clearer understanding of the complexity and diversity of these phages to be obtained. The isolation, sequencing and analysis of the hundreds of M. smegmatis bacteriophage genomes was performed by an integrated research and education program, called the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program. This enabled thousands of undergraduate students from different institutions to contribute to the phage discovery and sequencing project, and co-author the report. SEA-PHAGES therefore shows that it is possible to successfully incorporate genuine scientific research into an undergraduate course, and that doing so can benefit both the students and researchers involved.
The results show that while the genomes could be categorized into 28 clusters, the genomes are not completely unrelated. Instead, a spread of diversity is seen, as genes and groups of genes are shared between different clusters. Pope, Bowman, Russell et al. further reveal that the phage population is in a constant state of change, and continuously acquires genes from other microorganisms and viruses.
PMCID: PMC4408529  PMID: 25919952
bacteriophage; genomics; evolution; viruses
22.  Mycobacteriophages BPs, Angel and Halo: comparative genomics reveals a novel class of ultra-small mobile genetic elements 
Microbiology  2009;155(Pt 9):2962-2977.
Mycobacteriophages BPs, Angel and Halo are closely related viruses isolated from Mycobacterium smegmatis, and possess the smallest known mycobacteriophage genomes, 41 901 bp, 42 289 bp and 41 441 bp, respectively. Comparative genome analysis reveals a novel class of ultra-small mobile genetic elements; BPs and Halo each contain an insertion of the proposed mobile elements MPME1 and MPME2, respectively, at different locations, while Angel contains neither. The close similarity of the genomes provides a comparison of the pre- and post-integration sequences, revealing an unusual 6 bp insertion at one end of the element and no target duplication. Nine additional copies of these mobile elements are identified in a variety of different contexts in other mycobacteriophage genomes. In addition, BPs, Angel and Halo have an unusual lysogeny module in which the repressor and integrase genes are closely linked. The attP site is located within the repressor-coding region, such that prophage formation results in expression of a C-terminally truncated, but active, form of the repressor.
PMCID: PMC2833263  PMID: 19556295
23.  Comparative Genomics of Cluster O Mycobacteriophages 
PLoS ONE  2015;10(3):e0118725.
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.
PMCID: PMC4351075  PMID: 25742016
24.  Genome Sequence of Salmonella Phage χ 
Genome Announcements  2015;3(1):e01229-14.
Salmonella bacteriophage χ is a member of the Siphoviridae family that gains entry into its host cells by adsorbing to their flagella. We report the complete 59,578-bp sequence of the genome of phage χ, which together with its relatives, exemplifies a largely unexplored type of tailed bacteriophage.
PMCID: PMC4342425  PMID: 25720684
25.  Mycobacteriophages BPs, Angel and Halo: comparative genomics reveals a novel class of ultra-small mobile genetic elements 
Microbiology (Reading, England)  2009;155(Pt 9):2962-2977.
Mycobacteriophages BPs, Angel and Halo are closely related viruses isolated from Mycobacterium smegmatis, and possess the smallest known mycobacteriophage genomes, 41 901 bp, 42 289 bp and 41 441 bp, respectively. Comparative genome analysis reveals a novel class of ultra-small mobile genetic elements; BPs and Halo each contain an insertion of the proposed mobile elements MPME1 and MPME2, respectively, at different locations, while Angel contains neither. The close similarity of the genomes provides a comparison of the pre- and post-integration sequences, revealing an unusual 6 bp insertion at one end of the element and no target duplication. Nine additional copies of these mobile elements are identified in a variety of different contexts in other mycobacteriophage genomes. In addition, BPs, Angel and Halo have an unusual lysogeny module in which the repressor and integrase genes are closely linked. The attP site is located within the repressor-coding region, such that prophage formation results in expression of a C-terminally truncated, but active, form of the repressor.
PMCID: PMC2833263  PMID: 19556295

Results 1-25 (76)