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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 Thinking Like a Phage, tales of phage prowess are accompanied by pertinent electron micrographs; every chapter is enlivened by informative illustrations created by San Diego fine artist Leah PantEa. 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 – elude our everyday perception. Thinking Like a Phage offers a tour of this unseen dimension of life on Earth. Whether you are an expert or new to the phage world, these vignettes drawn from phage life will intrigue you. Awareness of this vast, creative, yet invisible realm can enrich your appreciation for the living world of which we, as Homo sapiens, are only a small part.
Preface vii
Acknowledgements ix
Chapter 1. Entering the World of Phage 1
Chapter 2. Survival on Arrival 61
Chapter 3. Production Management 87
Chapter 4. Architecture 101 109
Chapter 5. Escape! 157
Chapter 6. The Quest 185
Chapter 7. Special Delivery 215
Chapter 8. Coalition 241
Epilogue 271
Other Resources 273
Glossary 275
Index 290
Merry Youle's Abridged Bio 299
Leah L. Pantea is a classically trained artist who earned her BFA at Central Washington University and now specializes in drawing and painting. Her current mixed media abstract landscape work draws inspiration from the Abstract Expressionist movement.
"It took about 100 years of phage research for us to realize that phages (and viruses in general) dominate cellular life, there being 10 to 100 times more phages than hosts. Wherever hosts live, phages seem to be there, too. Phages were also front and center when the field of molecular biology emerged. These messages should be distributed to the entire biology-oriented public in an easily readable way. Youle's phage book certainly offers this opportunity. Very good for new comers and those who do not remember anymore."
– Dennis Bamford, Professor Emeritus, University of Helsinki
"Thinking Like a Phage is an engaging book that has the reader imagining what it is like to be a bacteriophage and to encounter the various challenges it faces, be it an obstinate cell wall, CRISPR fortifications, or a multitude of eager phage competitors. The range of depth and breadth of Thinking Like a Phage will delight every reader from the phage aphicianado to the student eager for immersion in the phascinating world of bacteriophages."
– Graham F. Hatfull, HHMI Professor, University of Pittsburgh
"Whether you are an advanced high school or college student, a general science enthusiast, or a an established researcher or biology teacher seeking stimulating ways to introduce concepts in the classroom, Thinking Like a Phage is enjoyable and informative reading. The author, Merry Youle, astutely chooses specific phages to illustrate key life-cycles stages, viral-host interactions, and evolutionary concepts. The writing is witty and engaging, yet technically accurate and thorough. Together, the original artwork and the enthusiastic prose produce an unusually refreshing scientific narrative."
– Bentley Fane, Professor, University of Arizona
"The phage phield has a nasty little secret: there is not a good introductory book for students and others interested in the most abundant life forms on the planet. Merry Youle has fixed this in the extraordinarily well-written Thinking Like a Phage. Concise, well-balanced in topics and current with the latest research, TLAP is a delight to read for the novice and expert alike. The incredible illustrations by Leah Pantea are both informative and beautiful. TLAP is the overview that the phage phield needs and a phascinating journey through the world's most interesting biology."
– Forest Rohwer, Professor, San Diego State University
"My students will enjoy reading scientific information that is presented in such a clear, interesting and exciting manner. Chapter 1 is the best introduction to bacteriophage biology I have seen yet – hits all of my favorite topics! The book spotlights many of the usual suspect phage that we don't talk a lot about but that I want my students to know exist, as well as some of the truly weirdo phage."
– Sally Molloy, Assistant Professor, University of Maine
"Our world is populated by untold numbers of creatures, but none are more abundant than the viruses that infect bacteria: the phages. This unseen realm plays a huge role in every ecosystem, yet its very existence is nearly universally unnoticed. It badly needs an advocate, and none serve better than Merry Youle. In these pages, she portrays this domain with aptly chosen examples, each described in an inviting, sometimes even witty, narrative. Be prepared to enter a splendid garden and view Nature at its most ingenious."
– Moselio "Elio" Schaechter, Distinguished Professor Emeritus, Tufts University School of Medicine
