Commentary: Why the world needs more than antibiotics to cure infections – CNA

LONDON: The world is in the midst of aglobal superbug crisis.

Antibiotic resistance has been found in numerous common bacterial infections, including tuberculosis, gonorrhoea and salmonellosis, making them difficult if not impossible to treat.

Were on the cusp of apost-antibiotic era, where there are fewer treatment options for such antibiotic-resistant strains. Given estimates that antibiotic resistance will cause10 million deaths a year by 2050, finding new methods for treating harmful infections is essential.

Strange as it might sound, viruses might be onepossible alternative to antibioticsfor treating bacterial infections. Bacteriophages (also known as phages) are viruses that infect bacteria.

Theyre estimated to be the most abundant organisms on Earth, with probably more than trillions of bacteriophages on the planet. They can survive in many environments, including deep sea trenches and the human gut.

While phages are efficient killers of bacteria, they dont infect human cells and are harmless to humans.

FIGHTING VIRUSES WITH VIRUS

Although phage therapy wasused in the 1930s, it has since become a forgotten cure in the West. Although the treatment became commonplace in the former Soviet Union, it wasnt adopted by western countries largely because of the discovery of antibiotics, which became widespread after World War II.

Bacteriophages are effective against bacteria because theyre able to attach themselves to the cell if they recognise specific molecules called receptors. This is the first step in the infection process. After attaching to the bacterial cell, the phage then injects its DNA inside the bacteria.

This causes one of two things to happen. After being injected with the phages DNA, the virus will take over the bacterial cells replication mechanism and start producing more phages.

This process is known as a lytic infection. This disintegrates the cell, allowing the newly produced viruses to leave the host cell to infect other bacterial cells.

But sometimes, the phage DNA gets incorporated into the bacterial hosts chromosome instead,becoming a prophage. It usually remains dormant but environmental factors, such as UV radiation or the presence of certain chemicals such asthose found in sunscreen, can cause the phage to wake up, start a lytic infection, take over the host cell and destroy it.

Lytic bacteriophagesare preferred for treatment because they dont integrate into the bacterial hosts chromosome.

But its not always possible to develop lytic bacteriophages that can be used against all types of bacteria. As each type of phage is only able to infect specific types of bacteria, they cant infect a bacterial cell unless the bacteriophage can find specific receptors on the bacterial cell surface.

However, engineering techniques can remove the bacteriophages ability to integrate into the hosts genome, making them useful for treatment.

Engineered phages have even successfully treated a drug-resistantMycobacterium abscessus infectionin a 15-year-old girl.

TARGETED TREATMENT

The reason bacteriophages are so effective against bacteria is because theyre only able to infect specific species. Antibiotics instead target a wide range of bacteria, including friendly bacteria not causing the infection.

But this also means that a single phage wont kill all strains of a disease-causing bacteria. And because bacteria areconstantly evolving, they can develop mechanisms that prevent phage infection. For example, if the bacterial cell has evolved and changed its surface receptors, the bacteriophage wont be able to attach itself and kill the bacteria.

As part of this evolutionary process, bacteria canrapidly become resistantto a single bacteriophage. But because there aremany types of bacteriophages, we can use a phage cocktail containing a combination of different bacteriophages totarget a broader rangeof bacterial strains within a species.

This decreases the chances a bacteria becomes resistant to all phages used in treatment. Bacteriophages can also be engineered toinfect more strainsof bacteria.

COMPLICATIONS DO EXIST

However, the presence of what are known asCRISPR systemsmight complicate the possibility of using bacteriophages in treatment. CRISPR is a bacterias natural defence system that allows it tobecome immuneto genetic material, such as phages, through infection, vaccination or the transfer of antibodies.

Bacteria may be resistant to bacteriophages if they have previously encountered similar types and developed immunity.

But bacteriophages have also developedanti-CRISPRproteins that can neutralise the host bacterias CRISPR systems.

This means a phage can still be effective, despite the presence of the bacterial CRISPR system. Not all bacteriophages have genes that neutralise anti-CRISPR proteins. But with the ability to engineer phage genomes, these could be incorporated into phages that are to be used for treatment in the future.

Although phage therapy isnt routinely used in western medicine, phage cocktails are available treatments in Russia and Georgia. Phage therapy is also acommon part of medical carein Georgia, especially in paediatric, surgical care and burns hospital settings.

Phages are used on their own or in combination with antibiotics and their use hasnt been linked to anyadverse effects.

With antibiotic-resistant infections becoming more common, bacteriophages offer the ability to treat such infections.

But forbacteriophages to become commonplacein treating bacterial infections, there needs to becontinued researchinto phage biology to better understand how they interact with bacteria.

Finding effective treatments for bacterial infections other than antibiotics is the first step in fighting further instances of antibiotic resistance.

Manal Mohammed IS Lecturer in Medical Microbiology at the University of Westminster. Andrew Millard is Lecturer in Bacteriophage Bioinformatics at the University of Leicester. This commentary first appeared in The Conversation.

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Commentary: Why the world needs more than antibiotics to cure infections - CNA