Phage Out

Abstract

Bacteria are microscopic single-celled organisms that lack a nucleus and membrane-bound organelles. Most bacteria have a protective cell wall, a cell membrane, and a strand of DNA. Many also have flagella to help them move, and all reproduce by binary fission, splitting into two new identical cells. Bacteria are highly diverse - they live in all types of environments on Earth and come in various shapes like rods or spirals. Of the three domains used to classify life, two are bacteria: Archaea and Eubacteria. Archaea bacteria have unique genes enabling them to get energy from ammonia, methane, and hydrogen gas. Most bacteria fall into the Eubacteria domain. While some bacteria can cause illness, most perform important functions - gut bacteria help digest food, cyanobacteria produce oxygen through photosynthesis, and bacteria are used to make foods like yogurt and cheese. In fact, bacterial cells make up 90% of the cells in the human body.

A virus is a microscopic infectious agent that consists of a strand of genetic material, either DNA or RNA, encased within a protein shell known as a capsid. Unlike living cells, viruses lack the cellular machinery necessary for self-replication - they require a host cell to infect and hijack in order to make copies of themselves. Viruses bind to specific receptors on the surface of host cells using proteins on their capsids, allowing them to gain entry. Once inside the cell, a virus will either inject its genetic material into the host cell cytoplasm or become fully engulfed into the cell. The viral genes then utilize the host cell's molecular mechanisms to produce numerous viral proteins and replicate the viral genome. These components self-assemble into new virus particles which accumulate inside the cell until the pressure causes the cell to burst, releasing a flood of viruses to infect surrounding cells. While some viruses are pathogenic and can cause disease, others have beneficial applications such as strengthening crop disease resistance or fighting cancer. Most remarkably, research suggests that ancient viruses infecting early bacteria may have provided the genetic material that led to the evolution of the nucleus within eukaryotic cells. In essence, the nucleus which defines all complex life may have originated from an ancient viral infection event.

Abundance and Distribution

Phages are extremely abundant in nature and play a critical ecological role in regulating bacterial populations. There are an estimated 10^31 phage particles on Earth, making them the most numerous biological entities. Phages can be found in all environments populated by bacterial hosts, including soil, seawater, the ocean depths, and the gut microbiomes of animals.

Each gram of human gut bacteria contains over 1 billion phage particles. Phages are equally diverse, with an estimated 10^31 different phage species globally. Different phages infect specific bacterial hosts, though some have broader host ranges. This phage diversity allows them to infect the full bacterial diversity.

What is the Historical Context?

Bacteriophages were first discovered in 1915 by Frederick Twort and in 1917 by Félix d’Hérelle, who realized their potential for killing bacteria. After an initial heyday in the pre-antibiotic era, phages were largely disregarded in Western medicine due to the ease of using antibiotics. However, phage research and application continued in some countries like the Soviet Union, where phages were routinely isolated and used therapeutically against bacterial infections. Much early phage research focused on model phages like T4 that infected Escherichia coli. These model systems laid the foundation of molecular biology, with phages helping identify DNA as the genetic material and the 3 nucleotide codon system. Phages also enabled discovery of restriction enzymes. For decades, only a handful of phages were studied in depth.

The recent resurgence of interest in phage biology stems from realizing just how abundant and diverse phages are in bacterial environments, as revealed by microscopy and bacterial genome sequencing. This belatedly showed phages shape many aspects of bacterial ecology and evolution. The patchy knowledge of phage biology accumulated over the past century demonstrates phages play critical roles across the natural world. These insights have sparked renewed interest in phage research, including development of phage therapy approaches to combat antibiotic resistant bacterial infections. After decades of obscurity, bacteriophages are now recognized as central players in microbial ecosystems and have potential as living antibiotics.