Archaeal Virus as Cat Toy

Stephen T. Abedon

Department of Microbiology – The Ohio State University

phage.org – phage-therapy.org – biologyaspoetry.org


 

This post is/was inspired by Stedman, K. M., M. DeYoung, M. Saha, M. B. Sherman, and M. C. Morais. 2015. Structural insights into the architecture of the hyperthermophilic fusellovirus SSV1. Virology 474:105-109. (ncbi.nlm.nih.gov/pubmed/25463608)

Turns out this spindle-shaped virus of Sulfolobus, potentially resembling “two fused fullerene cones”, is an almost perfect prolate spheroid, which (apparently) is the shape of a pig’s bladder, which in turn is the shape of the American football.

The virus itself, however, possesses a “hexameric tail”, which sort of looks like streamers emanating from one end of the “football”. And that, in turn, sure looks an awful lot like this, particularly were the tail trimmed:

http://www.entirelypets.com/jw-pet-cataction-football-streamers.html

“Art” imitates life belongs to cats!

For my renderings on this subject – archaeal virus as football – see:

https://www.facebook.com/pages/Bacteriophage-Ecology-Group/111721928901953

 

 

The ecology of viruses that infect eukaryotic algae

The world of algal viruses has only gotten more interesting in recent years as it has become increasingly clear just the sheer quantity of mortality they cause and how much that drives global nutrient cycling in ways we’ve been largely blind to.

Chlorovirus

The ecology of viruses that infect eukaryotic algae

Because viruses of eukaryotic algae are incredibly diverse, sweeping generalizations about their ecology are rare. These obligate parasites infect a range of algae and their diversity can be illustrated by considering that isolates range from small particles with ssRNA genomes to much larger particles with 560 kb dsDNA genomes. Molecular research has also provided clues about the extent of their diversity especially considering that genetic signatures of algal viruses in the environment rarely match cultivated viruses. One general concept in algal virus ecology that has emerged is that algal viruses are very host specific and most infect only certain strains of their hosts; with the exception of viruses of brown algae, evidence for interspecies infectivity is lacking. Although some host–virus systems behave with boom-bust oscillations, complex patterns of intraspecies infectivity can lead to host–virus coexistence obfuscating the role of viruses in host population dynamics. Within the framework of population dynamics, host density dependence is an important phenomenon that influences virus abundances in nature. Variable burst sizes of different viruses also influence their abundances and permit speculations about different life strategies, but as exceptions are common in algal virus ecology, life strategy generalizations may not be broadly applicable. Gaps in knowledge of virus seasonality and persistence are beginning to close and investigations of environmental reservoirs and virus resilience may answer questions about virus inter-annual recurrences. Studies of algal mortality have shown that viruses are often important agents of mortality reinforcing notions about their ecological relevance, while observations of the surprising ways viruses interact with their hosts highlight the immaturity of our understanding. Considering that just two decades ago algal viruses were hardly acknowledged, recent progress affords the optimistic perspective that future studies will provide keys to unlocking our understanding of algal virus ecology specifically, and aquatic ecosystems generally.

Data Storage and Standard Parts

Genetic data storage, scaleable cell-cell communication, and still-better gene expression, all thanks to phage!

Cross-talk between Diverse Serine Integrases

Abstract
Phage-encoded serine integrases are large serine recombinases that mediate integrative and excisive site-specific recombination of temperate phage genomes. They are well suited for use in heterologous systems and for synthetic genetic circuits as the attP and attB attachment sites are small (< 50 bp), there are no host factor or DNA supercoiling requirements, and they are strongly directional, doing only excisive recombination in the presence of a recombination directionality factor. Combining different recombinases that function independently and without cross-talk to construct complex synthetic circuits is desirable, and several different serine integrases are available. However, we show here that these functions are not reliably predictable, and we describe a pair of serine integrases encoded by mycobacteriophages Bxz2 and Peaches with unusual and unpredictable specificities. The integrases share only 59% amino acid sequence identity and the attP sites have fewer than 50% shared bases, but they use the same attB site and there is non-reciprocal cross-talk between the two systems. The DNA binding specificities do not result from differences in specific DNA contacts but from the constraints imposed by the configuration of the component half-sites within each of the attachment site DNAs.

New Applications for Phage Integrases

Within the last 25 years, bacteriophage integrases have rapidly risen to prominence as genetic tools for a wide range of applications from basic cloning to genome engineering. Serine integrases such as that from ϕC31 and its relatives have found an especially wide range of applications within diverse micro-organisms right through to multi-cellular eukaryotes. Here, we review the mechanisms of the two major families of integrases, the tyrosine and serine integrases, and the advantages and disadvantages of each type as they are applied in genome engineering and synthetic biology. In particular, we focus on the new areas of metabolic pathway construction and optimization, biocomputing, heterologous expression and multiplexed assembly techniques. Integrases are versatile and efficient tools that can be used in conjunction with the various extant molecular biology tools to streamline the synthetic biology production line.

21st Biennial Evergreen International Phage Meeting!

the-evergreen-state-college

You can register for the 21st Biennial Evergreen International Phage Meeting Aug. 2-7 on the Evergreen web site: www.evergreen.edu/phage.  If you register by April 30, you will qualify for the “Early Registration” rate: $600 for academics, $700 for Corporate Rate, $450 for graduate and undergraduate students and guests.  This covers all meeting costs, including room and board.  (If you choose to stay off campus, it will be $150 less, but still include meals.)  Some registration assistance is potentially available.

You will then have until May 24 to at least pay a $100 nonrefundable deposit, apply for assistance, or tell us that you are waiting for a visa.  If you register after May 1, the rates will be $100 more in each category.  Further meeting information is on the web site and will be regularly updated there.

Virologica Sinica special issue on “Phages and Therapy”

Note: Open access to this special issue no longer appears to be available…

2015, Volume 30, Issue 1

EDITORIAL

Bacteriophages, revitalized after 100 years in the shadow of antibiotics [pubmed]
Hongping Wei
In this issue, readers will not only find that bacteriophage research is a booming field but also learn about the diverse applications currently being explored for bacteriophages. The biggest driving force behind these applications is the serious threat of bacterial antibiotic resistance that is emerging in the current era.

REVIEWS

Bacteriophage secondary infection [pubmed]
Stephen T Abedon
Phages are credited with having been first described in what we now, officially, are commemorating as the 100th. anniversary of their discovery. Those one-hundred years of phage history have not been lacking in excitement, controversy, and occasional convolution. One such complication is the concept of secondary infection, which can take on multiple forms with myriad consequences. The terms secondary infection and secondary adsorption, for example, can be used almost synonymously to describe virion interaction with already phage-infected bacteria, and which can result in what are described as superinfection exclusion or superinfection immunity. The phrase secondary infection also may be used equivalently to superinfection or coinfection, with each of these terms borrowed from medical microbiology, and can result in genetic exchange between phages, phage-on-phage parasitism, and various partial reductions in phage productivity that have been termed mutual exclusion, partial exclusion, or the depressor effect. Alternatively, and drawing from epidemiology, secondary infection has been used to describe phage population growth as that can occur during active phage therapy as well as upon phage contamination of industrial ferments. Here primary infections represent initial bacterial population exposure to phages while consequent phage replication can lead to additional, that is, secondary infections of what otherwise are not yet phage-infected bacteria. Here I explore the varying meanings and resultant ambiguity that has been associated with the term secondary infection. I suggest in particular that secondary infection, as distinctly different phenomena, can in multiple ways infl uence the success of phage-mediated biocontrol of bacteria, also known as, phage therapy.

Bacteriophage therapy against Enterobacteriaceae [pubmed]
Youqiang Xu, Yong Liu, Yang Liu, Jiangsen Pei, Su Yao, Chi Cheng
The Enterobacteriaceae are a class of gram-negative facultative anaerobic rods, which can cause a variety of diseases, such as bacteremia, septic arthritis, endocarditis, osteomyelitis, lower respiratory tract infections, skin and soft-tissue infections, urinary tract infections, intra-abdominal infections and ophthalmic infections, in humans, poultry, animals and fi sh. Disease caused by Enterobacteriaceae cause the deaths of millions of people every year, resulting in enormous economic loss. Drug treatment is a useful and effi cient way to control Enterobacteriaceae infections. However, with the abuse of antibiotics, drug resistance has been found in growing number of Enterobacteriaceae infections and, as such, there is an urgent need to find new methods of control. Bacteriophage therapy is an efficient alternative to antibiotics as it employs a different antibacterial mechanism. This paper summarizes the history of bacteriophage therapy, its bacterial lytic mechanisms, and the studies that have focused on Enterobacteriaceae and bacteriophage therapy.

Survival and proliferation of the lysogenic bacteriophage CTXΦ in Vibrio cholerae [pubmed]
Fenxia Fan, Biao Kan
The lysogenic phage CTXΦ of Vibrio cholerae can transfer the cholera toxin gene both horizontally (inter-strain) and vertically (cell proliferation). Due to its diversity in form and species, the complexity of regulatory mechanisms, and the important role of the infection mechanism in the production of new virulent strains of V. cholerae, the study of the lysogenic phage CTXΦ has attracted much attention. Based on the progress of current research, the genomic features and their arrangement, the host-dependent regulatory mechanisms of CTXΦ phage survival, proliferation and propagation were reviewed to further understand the phage’s role in the evolutionary and epidemiological mechanisms of V. cholerae.

Phage lytic enzymes: a history [pubmed]
David Trudil
There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of ‘bacteria-eaters’ or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal fl ora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well (Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specifi c disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay (Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes-from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

RESEARCH ARTICLES

Selection of phages and conditions for the safe phage therapy against Pseudomonas aeruginosa infections [pubmed]
Victor Krylov, Olga Shaburova, Elena Pleteneva, Sergey Krylov, Alla Kaplan, Maria Burkaltseva, Olga Polygach, Elena Chesnokova
The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for the safe, long-term use of phage therapy against various infections caused by Pseudomonas aeruginosa. We describe the selection of the most suitable phages, their most effective combinations and some approaches for the rapid recognition of phages unsuitable for use in therapy. The benefi ts and disadvantages of the various different approaches to the preparation of phage mixtures are considered, together with the specifi c conditions that are required for the safe application of phage therapy in general hospitals and the possibilities for the development of personalized phage therapy.

Molecular dissection of phage lysin PlySs2: integrity of the catalytic and cell wall binding domains is essential for its broad lytic activity [pubmed]
Yanling Huang, Hang Yang, Junping Yu, Hongping Wei
The novel phage lysin PlySs2, is reported to be highly active against various bacteria, including staphylococci, streptococci and Listeria. However, the molecular mechanisms underlying its broad lytic spectrum remain to be established. In the present study, the lytic activity of the catalytic domain (CD, PlySc) and binding specificity of the cell wall binding domain (CBD, PlySb) of PlySs2 were examined. Our results showed that PlySc alone maintains very limited lytic activity. Enhanced green fluorescent protein (EGFP)-fused PlySb displayed high binding affinity to the streptococcal strains tested, including S. suis, S. dysgalactiae, and S. agalactiae, but not staphylococci, supporting its utility as a good CBD donor for streptococcal-targeted lysin engineering. EGFP-fused intact PlySs2 similarly displayed high affinity for streptococci, but not staphylococci. Notably, four truncated PlySb fragments showed no binding capacity. These fi ndings collectively indicate that integrity of the PlySc and PlySb domains is an essential determinant of the broad lytic activity of PlySs2.

Isolation and characterization of glacier VMY22, a novel lytic cold-active bacteriophage of Bacillus cereus [pubmed]
Xiuling Ji, Chunjing Zhang, Yuan Fang, Qi Zhang, Lianbing Lin, Bing Tang, Yunlin Wei
As a unique ecological system with low temperature and low nutrient levels, glaciers are considered a “living fossil” for the research of evolution. In this work, a lytic cold-active bacteriophage designated VMY22 against Bacillus cereus MYB41-22 was isolated from Mingyong Glacier in China, and its characteristics were studied. Electron microscopy revealed that VMY22 has an icosahedral head (59.2 nm in length, 31.9 nm in width) and a tail (43.2 nm in length). Bacteriophage VMY22 was classifi ed as a Podoviridae with an approximate genome size of 18 to 20 kb. A one-step growth curve revealed that the latent and the burst periods were 70 and 70 min, respectively, with an average burst size of 78 bacteriophage particles per infected cell. The pH and thermal stability of bacteriophage VMY22 were also investigated. The maximum stability of the bacteriophage was observed to be at pH 8.0 and it was comparatively stable at pH 5.0-9.0. As VMY22 is a cold-active bacteriophage with low production temperature, its characterization and the relationship between MYB41-22 and Bacillus cereus bacteriophage deserve further study.

LETTERS

Variation of resistance and infectivity between Pseudomonas fluorescens SBW25 and bacteriophage Ф2 and its therapeutic implications [pubmed]
Hanchen Chen, Guohua Chen
Studies of the coevolutionary dynamics between Pseudomonas fluorescens SBW25 and bacteriophage Ф can explore host resistance and parasite infectivity with applications in the ecological and therapeutic fields.Coevolutionary dynamics determine the efficacy of phage-based therapy. In the study described here, bacterial resistance and phage infectivity fluctuated with culturetime, perhaps resulting from random mutation and temporaladaptation, which reminds us of the necessity toconsider evolutionary mechanisms when applying phageto treat bacterial infections.

A novel transposable Mu-like prophage in Bacillus alcalophilus CGMCC 1.3604 (ATCC 27647) [pubmed]
Junjie Yang, Yimeng Kong, Xuan Li, Sheng Yang
In this letter, we provide evidence for the first transposable prophage BalMu-1 in Bacilli. The transposable prophage (BalMu-1, Genbank No. KP063902 and KP063903) was identified in Bacillus alcalophilus CGMCC 1.3604(ATCC 27647) through high throughput genome sequencing and PCR-dideoxy chain-termination(Sanger) sequencing.

Isolation and characterization of a lytic bacteriophage φKp-lyy15 of Klebsiella pneumoniae [pubmed]
Yinyin Lu, Hongyan Shi, Zhe Zhang, Fang Han, Jinghua Li, Yanbo Sun
In conclusion, the lytic bacteriophage φKp-lyy belonging to the Siphoviridae family specific for K. pneumonia was isolated and characterized. φKp-lyy displayed a short latent period, stability to a wide pH rang, high thermal resistance, and lytic activity toward a relatively broad range of K. pneumonia isolates. Thus, phage φKplyy should be considered as a candidate for inclusion in phage cocktails to control K. pneumoniae-associated nosocomial infections.

Expression and purification of recombinant lyase gp17 from the LSB-1 phage in Escherichia coli [pubmed]
Taiwu Wang, Hui Lin, Lu Zhang, Guorong Huang, Long Wu, Lei Yu, Hongyan Xiong
In this study, we successfully expressed and purified the recombinant gp17 protein from the LSB-1 phage and also confirmed its bacteriostatic effect. Assays also showed that the recombinant enzyme was soluble and had signifi cant lyase effects on the host bacterium, EIEC8401. A preliminary study demonstrated that the enzyme did not have inhibitory effects on other strains (unpublished data), which might indicate that the exclusive antibacterial effect of gp17 on EIEC8401 could have a special significance in practical application in bacterial therapy.

T4-like coliphage φKAZ14 virulent to pathogenic and extended spectrum β-lactamase-producing Escherichia coli of poultry origin [pubmed]
Kaikabo Adamu Ahmad, Abdulkarim Sabo Mohanmmed, Faridah Abas, Sieo Chin Chin
The aim of the present study was to isolate bacteriophages for the pre-harvest biocontrol of APEC 01 and ESBL-producing E. coli in chicken, in order to mitigate the risk of these pathogens to the food chain. Isolation and characterization of the T4-like coliphage KAZ14, lytic to APEC 01 and ESBL-producing E. coli, is reported and discussed.

Isolation and complete genome sequence of a novel virulent mycobacteriophage, CASbig [pubmed]
Tieshan Teng, Junping Yu, Hang Yang, Hongping Wei
In this study, we report the isolation and the complete genome of a novel mycobacteriophage, CASbig, which has an icosahedral head (diameter 50 ± 2 nm) and a long, non-contractile tail (length 160 ± 5 nm) with transverse striations, ending in a small knob. The length of the tail includes the middle of the baseplate, and the head measurements were taken between opposite apices. These characteristics indicate that the phage belongs to the family Siphoviridae morphotypes.

INSIGHT

Experience of the Eliava Institute in bacteriophage therapy [pubmed]
Mzia Kutateladze
The rapid propagation of multidrug resistant bacterial strains is leading to renewed interest in bacteriophage therapy. With challenges in the treatment of bacterial infections, it is essential for people worldwide to understand how alternative approaches, such as bacteriophages, could be used to combat antibiotic resistant bacteria. The Eliava Institute of Bacteriophages, Microbiology and Virology (Tbilisi, Georgia) is arguably the most famous institution in the world focused on the isolation, study, and selection of phages active against a variety of bacterial pathogens.

Phages vs. Potato Soft Rot

Stephen T. Abedon

Department of Microbiology – The Ohio State University

phage.org – phage-therapy.org – biologyaspoetry.org


 

Here’s an interesting news item, from only a couple of years back (April 4, 2013): “Taking a greener approach to managing potato spoilage”

http://www.farmersguardian.com/home/arable/arable-news/taking-a-greener-approach-to-managing-potato-spoilage/54554.article

Here are some quotes:

The innovative, eco-friendly product is called Biolyse and works by using naturally-occurring bacteriophage

APS chief executive Dr Alison Blackwell says now the product is proven to work on a large scale in potatoes, there is potential for it to be rolled out to other areas within the food processing industry.

Dundee-based APS has been developing bacteriophage since 2004.

Three years ago, APS received a Scottish Enterprise Research and Development grant and was then able to work closely with a team from Branston’s Abernethy site in Perthshire, Scotland, to identify the bacteria causing rots and develop a suitable bacteriophage.

Biolyse was launched in the Abernethy factory in November 2011 and rolled out across Branston’s other two sites in Lincolnshire and Somerset in 2012. The product is also used by QV Foods and Albert Bartlett.

There is a consistent five to tenfold reduction in rots pre and post bacteriophage treatment.

Installing the application equipment for Biolyse cost about £10,000 and was fairly simple, according to Kevin Imrie, site manager at Abernethy.

Anybody have any idea how this product currently is doing?

Here is APS Biocontrol’s web site: http://www.advancedpestsolutions.co.uk/

Further reading:

T4-related bacteriophage LIMEstone isolates for the control of soft rot on potato caused by ‘Dickeya solani’

Phage-Mediated Biocontrol of Plant Pathogens (2001 to “current”)

Phage therapy for plant disease control

Bacteriophage Ecology and Plants

 

E. coli, CRISPR, Biases in Our Understanding of Phage Ecology, and Possible Implications for Phage Therapy

Stephen T. Abedon

Department of Microbiology – The Ohio State University

phage.org – phage-therapy.org – biologyaspoetry.org


 

We’re all biased by what we know best and the link below discusses why, historically as well as microbiologically, we all “grew up” with the notion that envelope mutations are the primary means by which phage resistance evolves in bacteria. So thank you E. coli (I state with sarcasm):

http://schaechter.asmblog.org/schaechter/2014/11/why-crispr-doesnt-work-in-.html

What, I ask, are the implications for phage therapy of resistance mechanisms to specific phages that are essentially cost free and, at least arguably, Lamarckian as well, i.e., as due to CRISPR? For well-trained phage-therapy teams, I suspect not much. This is because, whether employing cocktails or monophages, the intention generally will be to hit bacterial targets hard and with whatever it takes to clear the infection, such as to switching phages during monophage therapy if resistance is noted.

But for monophages in the hands of less well-trained individuals, e.g., over-the-counter phage formulations or in the hands of poorly trained or regulated clinicians, the potential for development and then transmission of fully fit pathogens that nonetheless are fully resistant to a specific monophage could be fairly high. Importantly, and as relevant to the cited E. coi-CRISPR story, this issue may be more relevant for some pathogens, i.e., those with intact CRISPR systems, than it is for others.

So perhaps we can add inhibition of the potential for therapy-induced evolution of phage resistance among pathogens – as could then be transmitted across affected human communities – as an additional advantage of  prêt-à-porter (phage cocktails) versus sur-mesure (monophage therapy), while still retaining an argument for sur-mesure particularly among highly experienced phage therapists.

As we note in Chan and Abedon (2012), I nevertheless don’t buy arguments that spontaneously occurring phage host range mutations can be counted on in situ to counter bacterial evolution to phage resistance whether in the context of phage cocktails or instead monotherapy. From p. 19 of that publication:

A further consideration is that just as cocktails of phages may be thwarted in their ability to target low densities of phage-resistant bacteria, particularly given active treatment, these concerns should be even greater if one is relying on in situ phage evolution to supply resistance-countering phages… The reason for this is that the necessary host-range mutant phage types will be present in even lower densities than the phages explicitly found in cocktails. These same concerns may also be seen even in the absence of spatial structure so long as those phages within a cocktail that are amplified in situ, that is, in the course of active treatment, are not the same phages to which bacterial phage-resistant mutants are sensitive… Active therapy even with phage cocktails thus may be inherently incompatible with early interference with the evolution of bacterial resistance to phages.

 

Phage cocktails nevertheless should be better suited than monophages for dealing with evolving bacterial resistance to phages simply because cocktails inherently possess greater total numbers of phage particles that display divergent host ranges. On the other hand, the generation of cocktails of phages that display divergent host ranges – but where those phages nevertheless have been derived from a common genetic “platform” – might be expected to perform little better than monophages in the face of CRISPR-mediated phage resistance in target bacteria.

Further (Phage Therapy) Reading:

Chan, B. K., S. T. Abedon, and C. Loc-Carrillo. 2013. Phage cocktails and the future of phage therapy. Future.Microbiol. 8:769-783. [PubMed]

Chan, B. K. and S. T. Abedon. 2012. Phage therapy pharmacology: phage cocktails. Adv.Appl.Microbiol.  78:1-23. [PubMed]

Pirnay, J. P., V. D. De, G. Verbeken, M. Merabishvili, N. Chanishvili, M. Vaneechoutte, M. Zizi, G. Laire, R. Lavigne, I. Huys, G. Van den Mooter, A. Buckling, L. Debarbieux, F. Pouillot, J. Azeredo, E. Kutter, A. Dublanchet, A. Gorski, and R. Adamia. 2011. The phage therapy paradigm: prêt-à-porter or sur-mesure? Pharm.Res 28:934-937. [PubMed]

Importance of Specificity

Stephen T. Abedon

Department of Microbiology – The Ohio State University

phage.org – phage-therapy.org – biologyaspoetry.org


 

This article is not yet fully out but certainly is intriguing: http://www.cell.com/cell/abstract/S0092-8674(15)00003-3

The title is “Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease” by Norman et al.

The basic premise is that phages may very well be knocking out beneficial bacteria, in the gut, resulting in disease.

Here is a synopsis: https://www.sciencenews.org/article/when-bacteria-killing-viruses-take-over-it%E2%80%99s-bad-news-gut

To me what’s particularly interesting about this study, what little currently can be easily accessed, is that it actually can be viewed as an argument for the benefits of phage specificity in the guise of phage-mediated biocontrol of bacteria, i.e., phage therapy as applied clinically.

Specifically (if you will pardon the pun), when phages are employed in phage therapy, there is at best an only low potential that beneficial bacteria will be directly affected because phage host ranges tend to be quite narrow, typically at best spanning a single bacterial species and potentially some members of closely related genera. This contrasts with the typical antibiotic, which can be much less discriminatory in its impact on normal microflora, potentially resulting in bacterial superinfections.

Indeed, some antibiotics even can induce prophages, resulting in antibiotics potentially giving rise to excessive phage numbers that can impact beneficial bacteria. It is even possible for antibiotics to have an indirect impact by killing off certain bacteria that might then allow an overgrowth of beneficial bacteria which in turn could result in an achievement of so-called “winner” densities. Excessively high densities of specific bacterial types may then be followed by phage-induced reductions in the presence of these beneficial bacteria to below those levels present prior to antibiotic exposure (and then potentially overgrowth of harmful bacteria).

Sure these scenarios are complex and the latter certainly speculative. But the bottom line nonetheless is this: Some phages are bad – and we know this already since many phages carry bacterial virulence factor genes – but not all phages are bad, and those phages that are good in many or most instances probably give rise to somewhat less negative impact on the body than the majority of antibiotics.

Celebrate the diversity of phages, and their specificity!

Another layer of understanding to add to the genome injection story

Releasing the packaged viral DNA into the host cell is an essential process to initiate viral infection. In many double-stranded DNA bacterial viruses and herpesviruses, the tightly packaged genome is hexagonally ordered and stressed in the protein shell, called the capsid. DNA condensed in this state inside viral capsids has been shown to be trapped in a glassy state, with restricted molecular motion in vitro. This limited intracapsid DNA mobility is caused by the sliding friction between closely packaged DNA strands, as a result of the repulsive interactions between the negative charges on the DNA helices. It had been unclear how this rigid crystalline structure of the viral genome rapidly ejects from the capsid, reaching rates of 60,000 bp/s. Through a combination of single-molecule and bulk techniques, we determined how the structure and energy of the encapsidated DNA in phage λ regulates the mobility required for its ejection. Our data show that packaged λ-DNA undergoes a solid-to-fluid–like disordering transition as a function of temperature, resulting locally in less densely packed DNA, reducing DNA–DNA repulsions. This process leads to a significant increase in genome mobility or fluidity, which facilitates genome release at temperatures close to that of viral infection (37 °C), suggesting a remarkable physical adaptation of bacterial viruses to the environment ofEscherichia coli cells in a human host.

Significance

The efficiency of viral replication is limited by the ability of the virus to eject its genome into a cell. We discovered a fundamentally important mechanism for translocation of viral genomes into cells. For the first time, to our knowledge, we show that tightly packaged DNA in the viral capsid of a bacterial virus (phage λ) undergoes a solid-to-fluid–like structural transition that facilitates infection close to 37 °C. Our finding shows a remarkable physical adaptation of bacterial viruses to the environment of Escherichia coli cells in a human host.

In the beginning…

Young_d'Herelle“From a modern microbiological viewpoint the motivation behind the experiments that led to the discovery of bacteriophage is hard to understand. What was the purpose of filtering a bacterial culture to remove the bacteria, then remixing the filtrate with a fresh bacterial culture? We all know the outcome of this classic experiment, but why was it done in the first place? To fathom the intent of the original investigator, Félix d’Herelle, one has to put aside twenty-first century ideas and recover the context of microbiology and disease in the early twentieth century.