Thinking Like a Phage
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Thinking Like a Phage

The Genius of the Viruses That Infect Bacteria and Archaea

Merry Youle, Leah L Pantéa

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eBook - ePub

Thinking Like a Phage

The Genius of the Viruses That Infect Bacteria and Archaea

Merry Youle, Leah L Pantéa

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About This Book

It isn't easy to be a phage. First, what is a phage? A phage is a virus that infects Bacteria. To succeed, a phage must encounter, recognize, and enter a particular type of bacterial cell, then coerce it to make more phages rather than more cells. Of course, the cell resists this hostile takeover in numerous ways, all of which the successful phage overcomes. The triumphant phage then proceeds with its replicative business. In this engaging book, Merry Youle relates some of the tactics used by 21 pheatured phages to outwit their host and successfully maintain their own lineage generation after generation.

This ongoing contest of wits is a matter of life and death for both players. A phage chromosome arriving in its intended host cell is met by the cell's state-of-the-art defenses. Unless it dodges or neutralizes every one, it will be chopped into a nutritious snack for the cell. If the phage survives, it then quickly diverts the cell's machinery to production of more phages, rather than more cells. Under skillful phage supervision, manufacture of phage components proceeds at top speed, with all parts produced when needed and in the quantities required. As the pieces come off the assembly line, they self-assemble into sophisticated transport packages, each carrying a phage chromosome and capable of delivering it into a new host cell. When a new crop of progeny is ready – perhaps 25, 100, or more of them – the phage ruptures the cell to free them all and send them out into the world in quest of hosts of their own. Overall, a balance is maintained so that both the phages and their hosts thrive.

Many phages have the option to instead follow a different script. When they arrive in a host, they can opt to delay immediate hostile takeover and to instead form a coalition with the host for mutual benefit. In this case, as the cell grows and divides, the phage is replicated and inherited by both daughter cells. This can continue for many generations. However, if the cell encounters life-threatening difficulties, the phage ends the alliance and switches to rapid replication. Cell rupture and release of the new generation follows quickly.

Each step of the way presents challenges that test the ingenuity of the phages. In this book, tales of phage prowess are accompanied by pertinent electron micrographs; every chapter is enlivened by informative illustrations created by San Diego fine artist Leah Pantéa. The writing focuses on strategies and underlying principles, with a minimum of jargon. Since some knowledge of molecular biology is required to appreciate phage wizardry, a primer of the needed basics is provided for those unfamiliar with that subject. Thus, these phage adventures can be enjoyed by a wide audience.

Despite being the most abundant life form, the phages – being much smaller than even the microbes they infect –&th

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Chapter 1.
Entering the World of Phage

In which
we meet the phages and take note of their basic operating procedures. Each featured phage is individually introduced in the rogues’ gallery. Each is a wizard, a master of the intricacies of molecular biology. If you are not, if the basics of that field are not part of your background, you can nevertheless keep up with the phages if you first explore the primer provided here.
…it has been well said that a virus is “a piece of bad news wrapped up in protein.”
P.B. Medawar and J.S. Medawar, 1985
Whether or not viruses should be regarded as organisms is a matter of taste.
André Lwoff, 1962
Nevertheless, I believe that the virus factory should be considered the actual virus organism when referring to a virus.
Jean-Michel Claverie, 2006
Viruses are by common definition neither organisms nor alive.
Harald Bruüssow, 2009
Because, after all, a person’s a person, no matter how small.
Dr. Seuss, Horton Hears a Who
This is biology, so there are of course exceptions to any rules we might attempt to derive.
Sherwood Casjens, 2003
Two Points of View
Bobbing in mid-Pacific waves, or swirling in the roiling waters of an acidic hot spring, stuck in the mucus covering a coral polyp, ensconced in a crack in a desert rock, or trapped in the remains of an enchilada in your gut, a bacterium bursts open and 25, a hundred, perhaps a thousand multi-faceted jewels spill out from the carcassthe fruits of a successful phage infection. Riding the currents or ricocheting off cells and flotsam, these tiny hopeful particles disperse randomly, drifting. Occasionally a lucky one collides with a suitable bacterium and sticks. Then minutes, hours, days, or months later, this cell, too, ruptures and another horde ventures forth. The odds are against individual success, but the voyagers are many. If fortune smiles, one of them will arrive at an obliging door, will enter and dine, and will repeat this ancient cycle yet once again.
It’s a bacterium’s worst nightmare, the arrival of that one phage in a million who will evade all of its state-of-the-art defenses, who moreover arrives with a plan of its own, speaks the language understood by cellular machinery, and knows how to divert the cell’s energy and resources to virion production. This particular bacterium’s fate now is to support the multiplication of enemy troops and ultimately to release them into the neighborhood to prey upon its kin. Is its lineage doomed? It is, after all, out-numbered ten-to-one, and its family risks being out-maneuvered by the flagrant fecundity and rapid innovation of the phages. Not being so easily outdone, Bacteria meet the phage challenge again and again with innovations of their own, regaining the upper hand once more. Moreover, they can take some comfort in reminding themselves that the phages need them. Without hosts, the phages are at a dead end. Phage and host have co-existed for billions of years, the temporary advantage seesawing back and forth. Why worry? The cell continues to prepare to give birth to two daughters.
Whose side are you on?
What is a phage? That’s easy. It is a virus that infects a prokaryote. But now, instead of only one, we have three words to define: virus, infect, and prokaryote.
Virus is, at its root, a misnomer derived from the Latin vīrus, a poisonous liquid. An accurate and enduring definition was provided in 1978 by Salvador Luria, one of the key members of the phage group:1 Viruses are entities whose genomes are elements of nucleic acid that replicate inside living cells using the cellular synthetic machinery and causing the synthesis of specialized elements that can transfer the viral genome to other cells. Viruses are not the only entities now known to meet this definition. Therefore, this is often qualified further by noting that viral chromosomes2 travel from cell to cell enclosed in a protein shell, or capsid.
Infect refers to the entry of a viral chromosome into a living cell that it then manipulates to support its own replication.
Prokaryote is shorthand for the organisms that compose two of the three branches on the Tree of Life (see Figure 2). These two branches, originally known as the Bacteria and the Archaebacteria, were initially combined into one supergroup, the prokaryotes, because both groups are single-celled organisms without membrane-bounded intracellular compartments. Thus, diverse organisms were classified together based on what they lacked – a true nucleus and the other organelles found in all eukaryote cells. Genome sequencing later demonstrated marked differences in the cellular machinery and evolutionary histories of these two prokaryote branches. The Archaebacteria, renamed the Archaea, were then recognized as being a third distinct domain3 of life, as different from the Bacteria as either group is from the Eukarya.4
This definition of a phage is arguably correct, but it does not convey what makes the phages so fascinating, so intriguing, and so important. That is the job of the rest of this book and its planned sequel.
Figure 2: Tree of Life
It has long been debated whether or not viruses are alive. The answer depends on how you define life. A related argument flourishes today, this one questioning whether or not viruses should be included in the “universal” Tree of Life.5 This tree p...

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