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Bacteriophages and Archaeal Viruses as Living Biocides

4 hours ago
5 min read

One milliliter of seawater holds around ten million viruses, and almost none of them infect people, plants or animals. They infect microorganisms. Viruses that attack bacteria are called bacteriophages, or simply phages, from the Greek for "bacteria eater." Their counterparts that infect archaea are known as archaeal viruses. In the oceans alone, they kill a large share of the microbial population every day, releasing nutrients and shaping which species thrive. For anyone dealing with unwanted microbes in water systems, pipelines or reactors, that precision makes them interesting as living biocides.


Phages and archaeal viruses at a glance


A virus is a package of genetic material, DNA or RNA, wrapped in a protein shell called a capsid. It has no metabolism of its own. To multiply, it must attach to a host cell, deliver its genome and take over the cell’s machinery.


Frederick Twort and Félix d’Hérelle discovered phages independently in 1915 and 1917. Archaeal viruses came much later. Most of the known ones were isolated from the 1980s onward from hot, acidic springs and hypersaline lakes. David Prangishvili described many of the archaeal virus families known today, and his review “The enigmatic archaeal virosphere” remains a good overview of the field (Prangishvili et al., 2017). Patrick Forterre has shaped how researchers think about the role of viruses in evolution. Fewer than 100 archaeal viruses have been characterized in detail, compared with thousands of phages.


Host range is usually narrow. A given phage often infects a single species, sometimes only a few strains, because the fibers at the tip of its tail recognize specific receptors on the cell surface. That specificity is the main difference from chemical biocides, which hit everything in reach.


TEM image of a tailed virus isolate whose tail fibers bind specific receptors on the host cell surface
Tailed virus isolate with a long, flexible tail ending in host-recognition fibers

Lytic and lysogenic life cycles


Phages follow two main strategies, and some can switch between them.


  • Lytic cycle: the virus enters, replicates immediately and assembles new particles until the cell bursts, releasing tens to hundreds of progeny. Phage T4 infecting Escherichia coli is the classic example.


  • Lysogenic cycle: the viral genome integrates into the host chromosome, or persists as a plasmid, and is copied along with it at every cell division. This dormant form is called a prophage. Stress such as DNA damage can trigger a switch to the lytic cycle. Phage lambda is the textbook case.


  • Chronic infection: new particles are released continuously without killing the host, by extrusion or budding through the membrane. Filamentous phages such as M13 work this way.


Phages capable of lysogeny are called temperate, while those that only lyse are virulent. For biocide applications, virulent phages are preferred. A temperate phage can sit quietly inside its target and may even carry genes that make the host more robust.


Archaeal viruses tend toward the chronic end. Many establish long-term, stable infections and leave without lysing their host. Susanne Erdmann studies such infections in salt-loving archaea, including a virus that chronically infects the model organism Haloferax volcanii, and how hosts tolerate or fight off their viruses. Some archaeal viruses do lyse, using exit routes found nowhere else. Sulfolobus islandicus rod-shaped virus 2 (SIRV2) builds seven-sided pyramids on the cell surface that open outward like petals to release new particles. Tessa Quax described how these structures form and open (Quax et al., 2011), and Bertram Daum resolved their architecture with cryo-electron microscopy (Daum et al., 2014).


TEM image of a virus isolate with an angular capsid and long flexible tail, purified from an enrichment culture
Tailed virus isolate with an angular capsid and a long, flexible tail, purified by CsCl gradient

Unusual shapes


Most known phages share one basic design: a capsid that holds the genome and a tail that delivers it into the host. Within that design the variation is considerable. Capsids range from rounded to sharply angular, and under the electron microscope the icosahedral geometry often shows as a clear hexagonal outline. Tails can be short and straight or several times longer than the head. Some are rigid and contractile, pushing into the cell like a syringe, while others are long and flexible. A few phages have no tail at all. phiX174 is a plain icosahedron, and M13 is a long, thin filament.


TEM image of a virus isolate showing a hexagonal icosahedral capsid and short straight tail
Virus isolate with a clearly hexagonal icosahedral capsid and a short, straight tail

Archaeal viruses go much further. Several families have shapes not seen anywhere else in the viral world:


  • Spindle or lemon-shaped viruses, such as SSV1 from Saccharolobus (formerly Sulfolobus)


  • The bottle-shaped Acidianus bottle-shaped virus (ABV)


  • Droplet-shaped viruses of the family Guttaviridae


  • Acidianus two-tailed virus (ATV), which leaves its host as a tailless lemon shape and then grows two tails outside the cell at around 75 to 90 °C, with no host involved


  • Coil-shaped viruses of the family Spiraviridae 


Mart Krupovic has led much of the work classifying these viruses and tracing their evolutionary links to viruses of bacteria and eukaryotes. Many of their hosts live near boiling point at pH 2 to 3, so the particles have to stay intact in harsh conditions between infections.


The question of life


Whether viruses are alive depends on the definition, and there is no single accepted one. Textbook lists usually include metabolism, growth, reproduction, response to the environment and evolution. A working definition used by NASA describes life as a self-sustaining chemical system capable of Darwinian evolution.


Viruses pass some of these tests and fail others. They carry genes, mutate and evolve under selection. They cannot produce energy, synthesize proteins or reproduce outside a cell. On its own, a phage particle is inert.


Some researchers argue the particle is the wrong unit to judge. In the "virocell" concept proposed by Patrick Forterre, an infected cell becomes a different kind of organism dedicated to producing viruses, and that virocell is clearly alive. Giant viruses with genomes larger than those of some bacteria, and virophages that parasitize them, have blurred the line further. For practical purposes, "living biocide" fits well. Phages multiply where their target is present and fade out once it is gone.


Biotechnological applications


The best-known use is phage therapy. With antibiotic resistance rising, phages are being tested again against infections that no longer respond to drugs. In most Western countries this happens case by case under compassionate use, while Georgia and Poland have used phages clinically for decades. Other applications are already established:


  • Food safety: phage preparations against Listeria monocytogenes and Salmonella are approved for use on food in the US


  • Agriculture and aquaculture: control of plant pathogens and fish diseases


  • Molecular tools: phage display, recognized with the 2018 Nobel Prize in Chemistry, is used to develop therapeutic antibodies


  • Genome editing: CRISPR-Cas systems were first understood as bacterial and archaeal defenses against viruses before becoming editing tools


In industry, phages are being studied as a targeted alternative to chemical biocide treatment. Sulfate-reducing bacteria such as Desulfovibrio cause souring and microbially influenced corrosion in oil and gas systems, and lab studies have shown that phages can reduce their numbers and their hydrogen sulfide output. Phages can also work their way into biofilms, and some encode enzymes that degrade the matrix holding the cells together.


Archaeal viruses are at an earlier stage. Proposed uses include controlling methane-producing archaea in livestock digestion and using their highly stable capsids as scaffolds for nanomaterials.


The limitations are real. Narrow host range means a phage only works against the organism it was matched to, bacteria evolve resistance, and conditions such as temperature, salinity and pH affect how long phages persist. Any application starts with knowing exactly which microorganisms are present, then isolating the target hosts so candidate viruses can be tested against them.


Conclusion


Bacteriophages and archaeal viruses are the most abundant biological entities on Earth and among the most specific predators of microbes. Their life cycles and shapes are still being mapped, especially in extreme environments. That specificity is both their main limitation and the reason they are worth developing as living biocides.

 
 
 

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