Meet the editor

Renos Savva is a senior lecturer at Birkbeck, University of London. His research interests encompass the biological interactions of virus proteins, both with nucleic acids and with other proteins. Dr Savva's research concerns the nature of viral survival mechanisms, such as evasion of host restriction factors, and the adaptation and sequence plasticity of virus-encoded proteins. Dr Savva's published research includes insights from structural biology of

phage-encoded inhibitors of the ubiquitous Ung enzymes. His research furthermore addresses questions of protein sequence plasticity, which crosses over into synthetic biology collaborations: How adaptable are essential phage proteins, and what can be achieved in molecular engineering of phage particles and payloads? He also advocates for commercial translation of such fundamental insights for societal benefit.

Contents

and Their Synthetic Future

*by Helen E. White and Elena V. Orlova*

Scale-Up and Bioprocessing of Phages

in an Industrial Fermentation Process *by James A. Zahn and Mathew C. Halter*

*by Renos Savva*

*by Vitor B. Pinheiro*

*and Eli Keshavarz-Moore*

**Preface III**

**Chapter 1 1**

**Chapter 2 7**

**Chapter 3 39**

**Chapter 4 53**

**Chapter 5 77**

**Chapter 6 91**

**Chapter 7 109**

Biotechnology Tools Derived from the Bacteriophage/Bacteria Arms Race

Introductory Chapter: Nature's Ancient Nanomachines

Bacteriophages: Their Structural Organisation and Function

The Unusual Linear Plasmid Generating Systems of Prokaryotes

Surveillance and Elimination of Bacteriophage Contamination

Targeting Peptides Derived from Phage Display for Clinical Imaging

*by Sophie E. Knott, Sarah A. Milsom and Paul J. Rothwell*

*by John Maxim Ward, Steven Branston, Emma Stanley* 

*by Supang Khondee and Wibool Piyawattanametha*

## Contents


Preface

Bacteriophages are viruses that target and infect bacterial cells. As such, they have long attracted interest as potential therapeutic agents to control microbial pathogenesis. Since their discovery they have been proven to be promising antimicrobials, but caution has been mixed into that hope, because they are also capable of invoking pathogenicity in commensal and environmental species of bacteria. Study and cumulative knowledge of the ingenious factors that these viruses use to survive in the wild and to prevail over their host cells, has contributed greatly to many diverse

There is once again great promise that bacteriophages will play a prominent role in healthcare, not least fuelled by the rise in microbial antibiotic resistance globally. However, this hope also presents challenges. To understand the challenges, it is as well to also regard the problems bacteriophages could pose and how these can be solved. To realise their applied promise, bacteriophages will require production at unprecedented industrial scales. Exploring efficiency of mass production, as well as how to ensure purity from other bacteriophages that could contaminate medical-grade stocks, will be essential. In this volume, the chapters contributed respectively, by authors Zahn and Halter, and Ward et al., bring these matters into

In a wider healthcare context, the structural properties of bacteriophages become important factors for consideration. The chapter in this volume contributed by White and Orlova gives a detailed overview of what we know so far about the structure and mechanics of some of the better-known phage particle types. Engineering the surfaces of these viruses is a mature technology, but its deployment in personalised medical imaging is now technologically feasible and demonstrated as effective. The contributed chapter by Khondee and Piyawattanametha illuminates how surgery to remove metastatic tumours is given greater precision via engineered phage particle avidity. Exploiting the unusual properties of bacteriophage-encoded enzymes can allow new approaches in gene therapies and cell and tissue engineering. In fact, applications enabled by such unusual enzymatic activities could revolutionise data storage via biological macromolecules. The chapters contributed to this volume by Pinheiro, and the chapter by Knott, Milsom, and Rothwell, showcase unusual enzymatic processes which bacteriophages utilise for their adaptation and

Taking all these themes together, it is possible to envision bacteriophages as

ing bacteriophages can further enrich such endeavours.

potentially versatile nanoscale entities, with scope to be repurposed for a variety of interventions involving bacterial cells, or in entirely unrelated aims, encompassing aspects of healthcare and electronics. The macromolecular tools utilised by replicat-

facets of molecular biology and to the rise of synthetic biology.

focus.

survival.
