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Combating drug resistant bacteria with viruses

Pitting one against the other

Indiscriminate and uncontrolled use of antibiotics has lead to a situation where the bacteria are evolving immunity to various antibiotics at an alarming rate. In particular, gram negative bacteria, or bacteria with protective shields around them keep finding new ways of resisting treatment. Antibiotics find it hard to pass through the protective biofilm, covered by a sugary coating. They can pass on the genetic material to other bacteria, making them drug resistant as well. Early in 2017, the WHO identified twelve particularly harmful strains of bacteria. Some of the bacteria had developed resistance to the best antibiotic treatment options available, for tackling multi drug resistant bacteria. These bacteria are responsible for life threatening diseases including bloodstream infections and pneumonia.

What makes these bacteria particularly harmful, is that they tend to thrive and spread in an environment often visited by humans when their natural defenses are already weak – hospitals. The bacteria can spread through the devices used to treat patients, including ventilators and catheters. The UN has called for all countries to put policies in place for the responsible use of antibiotics. Around the world, from China to Portugal, multidrug resistant bacteria emerge from farm animals, because of antibiotic use as a growth promoters. The Centre for Science and Environment in India has asked the government for stronger control measures on antibiotic use, because of its rampant overuse in the poultry industry to make the chickens fatter. This has led to a high density of multi drug resistant bacteria in poultry farms, which can spread to humans as well. Irresponsible waste disposal has spread the bacteria to the environments around the poultry farms.

Research and development of new antibiotics cannot keep pace with the rate at which the bacteria are developing resistance. An emerging treatment option is the use of viruses to attack the harmful bacteria. Bacteriophages are viruses that infect bacteria, then reproduce within them.

Shortly before the advent of antibiotics in the 1940s, there was actually some research into the use of bacteriophages for treating diseases. However, the interest in the research ceased as the antibiotics proved to be a potent treatment, at least for a time. Now that the antibiotics are losing their effectiveness, there is a rekindled interest in the use of bacteriophages. The simplest and most direct approach is to identify bacteriophages, to isolate them, and to administer them as necessary. In nature, bacteriophages are found in high numbers wherever the bacteria exist.

Bacteriophages are highly specific to particular species or families of bacteria. They are harmless to the humans, and also to other beneficial bacteria within humans. Antibiotics tend to take down beneficial bacteria as well. The treatment options can be designed to target specifically the harmful bacteria. If there is more than one strain causing an infection, a combination of bacteriophages, or bacteriophage cocktails can be administered as required.

Just as bacteria evolved resistance to antibiotics, they can evolve resistance to phages as well. This evolution can happen during the treatment itself, before the pathogen is eliminated from the host body. The advantage of using viruses is that as living organisms, they have the capacity to evolve approaches to counter the resistance of the bacteria.

There are a handful of companies working on the approach on another approach, bioengineered bacteriophages that are particularly effective at killing the target bacteria.

Within bacteria, are DNA sequences that are collectively known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR is a natural defense mechanism for the bacteria, and contain portions of DNA from the bacteriophages, that help the bacteria identify and eliminate the viruses. Bioengineered bacteriophages infect the target bacteria, and modify the CRISPR system, prompting the bacteria to use its natural defenses to destroy itself. One approach for these modified bacteriophages involves completely removing the ability for the bacteriophage to replicate at all. The bacterial immune system is essentially repurposed to cause the pathogen to self destruct.

The challenges involve identifying the bacteria in the host organism, and modifying the phages to target the bacteria. Different regions may require different phages, depending on the local strains of bacteria. Regulation is another problem as the treatment involves living, evolving creatures. As living organisms, it is difficult for pharmaceutical companies to patent the bacteriophages, and as such the commercial corporations may be unwilling to fund research into bacteriophage treatment options.

Human trials are expected to begin in Europe within the next two years. As the capacity for antibiotics to tackle bacteria reduces, there is expected to be an increasing reliance on bacteriophages for treating infections. Treatments in the future will possibly include a combination of naturally occurring and bioengineered bacteriophages.

Aditya Madanapalle

Aditya Madanapalle

An avid reader of the magazine, who ended up working at Digit after studying journalism, game design and ancient runes. When not egging on arguments in the Digit forum, can be found playing with LEGO sets meant for 9 to 14-year-olds.