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Bacteriophages

Bacteria-infecting viruses. The lytic and lysogenic cycles.

Introduction

Even bacteria can get a virus! The viruses that infect bacteria are called bacteriophages, and certain bacteriophages have been studied in detail in the lab (making them some of the viruses we understand best).
In this articles, we'll take a look at two different cycles that bacteriophages may use to infect their bacterial hosts:
  • The lytic cycle: The phage infects a bacterium, hijacks the bacterium to make lots of phages, and then kills the cell by making it explode (lyse).
  • The lysogenic cycle: The phage infects a bacterium and inserts its DNA into the bacterial chromosome, allowing the phage DNA (now called a prophage) to be copied and passed on along with the cell's own DNA.
Let's take a closer look at each of these cycles.

A bacteriophage is a virus that infects bacteria

A bacteriophage, or phage for short, is a virus that infects bacteria. Like other types of viruses, bacteriophages vary a lot in their shape and genetic material.
  • Phage genomes can consist of either DNA or RNA, and can contain as few as four genes or as many as several hundredstart superscript, 1, comma, 2, comma, 3, end superscript.
  • The capsid of a bacteriophage can be icosahedral, filamentous, or head-tail in shape. The head-tail structure seems to be unique to phages and their close relatives (and is not found in eukaryotic viruses)start superscript, 4, comma, 5, end superscript.
    Icosahedral phage, head-tail phage, and filamentous phage.
    Image modified from "Corticovirus," "T7likevirus," and "Inovirus, by ViralZone/Swiss Institute of Bioinformatics, CC BY-NC 4.0.

Bacteriophage infections

Bacteriophages, just like other viruses, must infect a host cell in order to reproduce. The steps that make up the infection process are collectively called the lifecycle of the phage.
Some phages can only reproduce via a lytic lifecycle, in which they burst and kill their host cells. Other phages can alternate between a lytic lifecycle and a lysogenic lifecycle, in which they don't kill the host cell (and are instead copied along with the host DNA each time the cell divides).
Let's take closer look at these two cycles. As an example, we'll use a phage called lambda (lambda), which infects E. coli bacteria and can switch between the lytic and lysogenic cycles.

Lytic cycle

In the lytic cycle, a phage acts like a typical virus: it hijacks its host cell and uses the cell's resources to make lots of new phages, causing the cell to lyse (burst) and die in the process.
  1. Attachment: Proteins in the "tail" of the phage bind to a specific receptor (in this case, a sugar transporter) on the surface of the bacterial cell.
  2. Entry: The phage injects its double-stranded DNA genome into the cytoplasm of the bacterium.
  3. DNA copying and protein synthesis: Phage DNA is copied, and phage genes are expressed to make proteins, such as capsid proteins.
  4. Assembly of new phage: Capsids assemble from the capsid proteins and are stuffed with DNA to make lots of new phage particles.
  5. Lysis: Late in the lytic cycle, the phage expresses genes for proteins that poke holes in the plasma membrane and cell wall. The holes let water flow in, making the cell expand and burst like an overfilled water balloon.
Cell bursting, or lysis, releases hundreds of new phages, which can find and infect other host cells nearby.
Image modified from "Conjugation," by Adenosine (CC BY-SA 3.0). The modified image is licensed under a CC BY-SA 3.0 license. Based on similar diagram in Alberts et al.start superscript, 6, end superscript
The stages of the lytic cycle are:
  1. Attachment: Proteins in the "tail" of the phage bind to a specific receptor (in this case, a sugar transporter) on the surface of the bacterial cell.
  2. Entry: The phage injects its double-stranded DNA genome into the cytoplasm of the bacterium.
  3. DNA copying and protein synthesis: Phage DNA is copied, and phage genes are expressed to make proteins, such as capsid proteins.
  4. Assembly of new phage: Capsids assemble from the capsid proteins and are stuffed with DNA to make lots of new phage particles.
  5. Lysis: Late in the lytic cycle, the phage expresses genes for proteins that poke holes in the plasma membrane and cell wall. The holes let water flow in, making the cell expand and burst like an overfilled water balloon.
Cell bursting, or lysis, releases hundreds of new phages, which can find and infect other host cells nearby. In this way, a few cycles of lytic infection can let the phage spread like wildfire through a bacterial population.

Lysogenic cycle

The lysogenic cycle allows a phage to reproduce without killing its host. Some phages can only use the lytic cycle, but the phage we are following, lambda (lambda), can switch between the two cycles.
In the lysogenic cycle, the first two steps (attachment and DNA injection) occur just as they do for the lytic cycle. However, once the phage DNA is inside the cell, it is not immediately copied or expressed to make proteins. Instead, it recombines with a particular region of the bacterial chromosome. This causes the phage DNA to be integrated into the chromosome.
Lysogenic cycle:
  1. Attachment. Bacteriophage attaches to bacterial cell.
  2. Entry. Bacteriophage injects DNA into bacterial cell.
  3. Integration. Phage DNA recombines with bacterial chromosome and becomes integrated into the chromosome as a prophage.
  4. Cell division. Each time a cell containing a prophage divides, its daughter cells inherit the prophage.
Image modified from "Conjugation," by Adenosine (CC BY-SA 3.0). The modified image is licensed under a CC BY-SA 3.0 license. Based on similar diagram in Alberts et al.start superscript, 6, end superscript
The integrated phage DNA, called a prophage, is not active: its genes aren't expressed, and it doesn't drive production of new phages. However, each time a host cell divides, the prophage is copied along with the host DNA, getting a free ride. The lysogenic cycle is less flashy (and less gory) than the lytic cycle, but at the end of the day, it's just another way for the phage to reproduce.
Under the right conditions, the prophage can become active and come back out of the bacterial chromosome, triggering the remaining steps of the lytic cycle (DNA copying and protein synthesis, phage assembly, and lysis).
  1. Prophage exits chromosome and becomes its own circularized DNA molecule.
  2. Lytic cycle commences.
Image modified from "Conjugation," by Adenosine (CC BY-SA 3.0). The modified image is licensed under a CC BY-SA 3.0 license.

To lyse or not to lyse?

How does a phage "decide" whether to enter the lytic or lysogenic cycle when it infects a bacterium? One important factor is the number of phages infecting the cell at oncestart superscript, 9, end superscript. Larger numbers of co-infecting phages make it more likely that the infection will use the lysogenic cycle. This strategy may help prevent the phages from wiping out their bacterial hosts (by toning down the attack if the phage-to-host ratio gets too high)start superscript, 10, end superscript.
What triggers a prophage to pop back out of the chromosome and enter the lytic cycle? At least in the laboratory, DNA-damaging agents (like UV radiation and chemicals) will trigger most prophages in a population to re-activate. However, a small fraction of the prophages in a population spontaneously "go lytic" even without these external cuesstart superscript, 7, comma, 11, end superscript.

Bacteriophage vs. antibiotics

Before antibiotics were discovered, there was considerable research on bacteriophages as a treatment for human bacterial diseases. Bacteriophages attack only their host bacteria, not human cells, so they are potentially good candidates to treat bacterial diseases in humans.
After antibiotics were discovered, the phage approach was largely abandoned in many parts of the world (particularly English-speaking countries). However, phages continued to be used for medical purposes in a number of countries, including Russia, Georgia, and Poland, where they remain in use todaystart superscript, 12, comma, 13, end superscript.
There is increasing interest in bringing back the "phage approach" elsewhere, as antibiotic-resistant bacteria become more and more of a problem. Research is still needed to see how safe and effective phages are, but who knows? One day, your doctor might write you a prescription for phages instead of penicillin!

Want to join the conversation?

  • spunky sam blue style avatar for user ibrahim
    i thought the antibiotic killing bacteria and viruses. but why the antibiotic kill only viruses? (that what i understood)
    (5 votes)
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    • male robot hal style avatar for user Charles LaCour
      Antibiotics only work on bacteria not viruses. Antibiotics work on specific processes in the life cycle of the bacteria that either kill the bacteria or stop it from replicating. Viruses use the host cells to replicate so the antibiotics do not affect the viruses life cycle.
      (38 votes)
  • piceratops seed style avatar for user John Daniel Briones
    If it's true that 8 percent of our genome were from viruses that merged with our eukaryotic ancestors, could that viral DNA be the seed for cancer in all of us?
    (7 votes)
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    • duskpin ultimate style avatar for user fiqx007
      That also made me think about mitochondrial diseases. There's this endosymbiotic theory where they said mitochondria and chloroplast were descendant of ancient prokaryotes organism that developed a symbiotic relationship with the progenitor eukaryotic cells. So, could it be that the ancient prokaryote cell infected with bacteriophage that causes what we have today the mitochondrial diseases? I'm still new to these topic so I don't know much.
      (5 votes)
  • male robot hal style avatar for user John Kamwithi Githuga
    When a phage injects its double stranded DNA to a host does it still remain a phage or does it still has some other DNA strands to qualify being a phage?
    (7 votes)
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  • blobby green style avatar for user FATEMA Taher
    what about the classification of bacteriophage? ..how is it classified and what are the differences between their kinds
    (2 votes)
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  • blobby green style avatar for user arintalabany
    So which cycle replicates the virus faster and which one is more dangerous ?
    (3 votes)
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  • hopper jumping style avatar for user A person
    what potential dangers could phages even have? Will it accidentally evolve and target human cells?
    (2 votes)
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  • mr pants teal style avatar for user aditya.singh6170
    if phage DNA recombine with chromosome and make its copies then is it living process or non living
    (2 votes)
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  • orange juice squid orange style avatar for user Koketso Ramotsila
    forms of immunity used by prokaryotes to protect themselves from viral DNA
    (2 votes)
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  • male robot hal style avatar for user Michael Zero
    In comparison to antibiotics, bacteriophages seem like more precision-guided weapons than the clunky antibiotics that affect both the infectious cells and healthy cells. But if we start using bacteriophages more commonly to fight infection, how can we determine if the bacteriophages will attack only the infectious cells? Is it common for bacteriophages to attack multiple kinds of cells, or do they generally only affect one type? If we use a bacteriophage to attack chlamydia, for example, how likely are we to see the bacteriophage attack only the chlamydia bacteria and not normal human cells or desirable bacteria in the pelvis?
    (2 votes)
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  • blobby green style avatar for user 😊
    how long it takes to bacteriophage to enter the bacteria?
    (2 votes)
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