Phages to Combat Antibiotic Resistance

The misuse of antibiotics causes selective pressure, so that bacteria become stronger and more persistent. This is a serious problem and phage therapy could be the solution.
Phages to Combat Antibiotic Resistance

Last update: 11 June, 2021

We must combat antibiotic resistance as it’s a serious problem for public health. Phages can come to the rescue in an attempt to solve the problem.

The abuse of these drugs and their misuse are among the main reasons why bacteria undergo mutations and acquire multidrug-resistant genes. This ability helps them to escape the effects of antibiotics, proliferating and growing in their presence.

Here we’ll tell you about one of the most interesting therapies used to fight against this problem.

What is a bacteriophage?

A bacteriophage, also known as a phage, is a virus that infects and kills bacteria. It has genetic material, which can be DNA or RNA, protected by a capsid.

When it encounters a bacterium, it interacts with it, binding to specific receptors on its surface. There it injects its genome into the bacterial cell. At this moment, two life cycles can take place:

  • Lytic cycle: phages act like a typical virus. They use the bacterial machinery to multiply and release new phages, resulting in the death of the bacterium.
  • Lysogenic cycle: the genetic material of the phage is integrated into the genome of the host cell, so that the phage will reproduce without killing it. When the bacterium divides, it will make copies of its genetic material together with that of the phage, so that the phage will be in future descendant cells.

Phages are microorganisms found in all ecosystems on Earth. In addition, we find them in the oceans, in the air and inside the human body.

They’re found regulating bacterial populations. Thanks to them, bacterial microbiota remain stable and balanced in living organisms.

They’re also considered to be the most abundant organisms on our planet, so much so that in 1989 Norwegian scientists found 250 million phages in one milliliter of seawater.

a virus
Phages are viruses that infect bacteria, and could be used when to combat antibiotic resistance.

The use of phages against infectious diseases

Scientists have been using these particles as therapies against epidemics for years. Félix d’Hérelle was a microbiologist, and the first to coin the term bacteriophage, meaning “bacteria-eater”.

He invented phage therapy after using phages to treat bacterial infections. In the cholera epidemic in India in 1927, he treated patients with phages and succeeded in reducing the mortality rate from 60% to 8%.

Although years earlier, in 1921, doctors already used phages orally in patients in a Paris hospital suffering from toxic dysentery and managed to recover. They also used them to treat typhoid fever, skin infections, urinary tract infections and otitis externa.

A century later we’re still rethinking, why not use them to kill multidrug-resistant bacteria or as substitutes for antibiotics?

Phage therapy

In this alternative to antibiotics, doctors use phages with the aim of killing bacteria that are causing infection in a patient. One of the fundamental requirements is the use of lytic phages to ensure bacterial killing and elimination of toxic bacterial compounds.

The use of combined phage therapies with other phages, antibiotics or vaccines is effective in reducing the likelihood of generating resistance.

Why use bacteriophages?

Bacteria antibiotics
Bacterial resistance has one of its origins in antibiotic abuse.

We must remember that phages are viruses, and therefore scientists don’t consider them living organisms. However, they’re dynamic entities, and the lytic cycle is the key to phage therapy.

Antibiotics, on the other hand, are chemicals that act by disrupting specific bacterial processes. In addition, they can disrupt protein synthesis or cell wall manufacture.

These are some of the advantages of phage therapy over the use of antibiotics:

  • Bacterial specificity: phages only infect specific bacterial strains, leaving the rest intact and without damaging the flora of the medium where the treatment is being applied. Thus, they don’t cause microbiota disorders, such as antibiotic-associated diarrhea or candidiasis in the mucous membranes.
  • Autodosing: bacteriophages increase their population where they’re infecting. In this way we don’t have to administer them repeatedly. In addition, the phages disappear automatically as they have no more hosts to infect.
  • Different mechanisms of action: this allows us to treat infectious diseases caused by multi-resistant bacteria for which antibiotics aren’t effective.

Future lines of research

The discovery of phages, more than a century ago, has allowed us to advance in the understanding of numerous biological processes, as well as to design new genetic techniques. Their use is increasing and, therefore, it’s time to invest time and money in their research.

As with antibiotics, the use of lytic phages causes selective pressures. So this leads to the proliferation of bacteria with mutations that make them resistant to phages. However, this is a challenge that still needs to be studied in depth.

In conclusion, we must continue research to close this gap and advance in the use of new therapies in order to combat the great threat posed by antibiotic resistance.

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