For Beginners : Where Do Bacteriophages Come From? A Scientific Exploration of Their Natural Origins and Discovery

Where Do Bacteriophages Come From? 

A Scientific Exploration of Their Natural Origins and Discovery

Bacteriophages, or simply phages, are viruses that infect and kill bacteria. Far from being rare or exotic, they are among the most abundant and diverse biological entities on Earth. Despite their microscopic size, their influence spans from the oceanic depths to the human microbiome. Understanding where phages originate and how they are discovered reveals not only their ecological importance but also their potential as therapeutic tools in the age of antibiotic resistance.

Bacteriophages exist wherever bacteria thrive. This means they are present in virtually every ecosystem: soil, freshwater, marine environments, sewage, and the intestines of animals, including humans. In fact, it is estimated that there are around 10³¹ phages on the planet—ten million trillion trillion—making them more numerous than all other organisms combined (Hatfull, 2008). These viral particles are constantly at work, shaping microbial populations, controlling bacterial blooms, and contributing to genetic exchange via horizontal gene transfer.

One of the richest sources of phages is wastewater. Municipal sewage, teeming with diverse bacterial communities, provides an ideal environment for phages to evolve. Scientists frequently sample raw sewage to isolate novel phages, particularly those that infect clinically relevant bacteria such as Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa. The advantage of sewage is its bacterial diversity, which drives a corresponding diversity of phages. In one study conducted by researchers at Yale University, over 500 unique phages were isolated from just a few liters of untreated wastewater (Kortright et al., 2019).

                             

Artistic view

Soil is another prolific reservoir of phages, especially in areas rich in organic matter. In agricultural soil, for example, the phage-to-bacterium ratio can exceed 10:1. These phages play crucial roles in nutrient cycling and disease suppression in plants. They also serve as a hidden archive of viral biodiversity. In one metagenomic analysis of forest soil, over 40,000 putative viral sequences were identified, many of which were novel and lacked homology with known phages (Paez-Espino et al., 2016).

The human body itself is a complex habitat for phages. The gut virome—comprising viruses found in the gastrointestinal tract—is dominated by phages, particularly those belonging to the Caudovirales order and the Microviridae family. A healthy adult gut can harbor between 10⁹ and 10¹⁰ phage particles per gram of feces (Shkoporov & Hill, 2019). These resident phages modulate the microbiome, affect bacterial community structure, and are thought to play roles in immune regulation.

Collecting and identifying phages involves a combination of classical microbiology and modern genomics. Researchers begin by collecting a sample from a chosen environment—wastewater, soil, feces, or seawater. The sample is filtered to remove bacteria and debris, and then enriched with a specific bacterial host in liquid culture. If phages targeting the host are present, they will infect and lyse the bacteria, producing a clear zone known as a plaque on agar plates. These plaques can be isolated and purified for further analysis.

Once isolated, phages are characterized using transmission electron microscopy, genome sequencing, and host-range assays. The recent integration of high-throughput sequencing and machine learning has allowed for the rapid identification of phage genomes, many of which do not resemble any previously known viruses. In a 2021 effort led by the Tara Oceans expedition, over 200,000 new viral species were discovered across the world's oceans, with phages comprising a significant proportion (Brum et al., 2015; Gregory et al., 2021).

The discovery process is often likened to a scientific treasure hunt. Each environmental sample holds the possibility of uncovering a completely novel virus with unique properties. Because phages evolve in tandem with their bacterial hosts, they are constantly changing, meaning that even familiar environments like sewage or soil can yield previously unobserved phage types. This dynamic relationship ensures a nearly endless frontier for exploration.

Understanding the natural origins of phages is essential for therapeutic development. Environmental samples provide the raw material for creating phage libraries, which are then screened for activity against antibiotic-resistant pathogens. For example, the Eliava Institute in Georgia has maintained a phage collection sourced from diverse ecosystems for over 90 years, using these isolates to treat infections with remarkable success.

In conclusion, phages are ubiquitous, ancient, and immensely diverse. They inhabit every corner of the biosphere where bacteria exist. From ocean currents to hospital drains, their presence is both universal and essential. Their discovery, once driven by serendipity, is now guided by systematic approaches and advanced tools. As phage therapy gains traction as a viable alternative to antibiotics, the environments in which phages naturally reside will remain a primary source of biomedical innovation.

References:

• Hatfull, G. F. (2008). Bacteriophage genomics. Current Opinion in Microbiology, 11(5), 447–453.

• Kortright, K. E., Chan, B. K., Koff, J. L., & Turner, P. E. (2019). Phage therapy: A renewed approach to combat antibiotic-resistant bacteria. Cell Host & Microbe, 25(2), 219–232.

• Paez-Espino, D., et al. (2016). Uncovering Earth's virome. Nature, 536(7617), 425–430.

• Shkoporov, A. N., & Hill, C. (2019). Bacteriophages of the human gut: The “known unknown” of the microbiome. Cell Host & Microbe, 25(2), 195–209.

• Brum, J. R., et al. (2015). Patterns and ecological drivers of ocean viral communities. Science, 348(6237), 1261498.

• Gregory, A. C., et al. (2021). Marine DNA viral macro- and microdiversity from pole to pole. Cell, 177(5), 1109–1123.e14.