Resistance Is Futile!!!

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You hear stories about it in the news weekly, but just what is antibiotic resistance, and is the future of antibiotic era of healthcare as vulnerable as we are lead to believe?

Antibiotic resistance is arguably one of the biggest global problems facing humans today. Without a way to defend ourselves against diseases, we hardly even give a second thought to how we could be plunged back into a situation similar to that of the ‘pre-antibiotic era’.

Since Alexander Fleming pioneered the development of antibiotics with his accidental discovery of penicillin in 1928, we have grown dependent on these drugs.

‘antibiotic resistance is arguable one of the biggest global problems facing humans today’

They have revolutionised medicine, increasing the US expected lifespan from 56 in 1920 to 79 years now, and penicillin alone is estimated to have saved at least 200 million lives. But, due to several factors such as overuse and livestock use, bacteria have developed resistance to these antibiotics.

Antibiotic resistance is the ability for a bacteria to be able to survive in the presence of an antibacterial agent that was originally effective against treating infections of it, such as penicillins.

This is effectively accelerated evolution, as the presence of an antibiotic ensures only resistant bacteria survive, and then pass on their resistive genes to their daughter cells.

This process, known as vertical gene transfer (VGT), rapidly spreads resistance throughout the bacterial population, as some bacteria (such as E. coli) can double the size of their population in just 20 minutes.

Bacteria also have the unique skill to be able to pass their genetic information to nearby bacteria. Termed horizontal gene transfer (HGT), this skill can even transfer resistive genes to other species of bacteria, making the resistance much more significant as it only has to arise once. This is the primary mechanism of how resistance spreads throughout the population – more so than VGT.

But antibiotic resistance isn’t even a new occurrence. In 2011, a team lead by researchers at McMaster University in Canada found evidence of resistance to three common antibiotics in 30,000 year old sediments. So if it isn’t novel, why is it becoming an increasing problem?

The main reason is the incorrect usage of antibiotics. It can be difficult to diagnose the specific bacterial species causing an infection, meaning that the most effective drug might not be prescribed, pushing bacteria forwards in the arms race between us and them.

New diagnostic tools are in development, which, if accurate would allow us to give the most appropriate drug, also reducing the side effects experienced.

Another reason is that people don’t always complete the full course of their treatment for their infection as recommended, meaning that not all bacterial cells are killed. This leads to persistent and recurrent infections, as those surviving cells have a longer chance to develop resistance to the antibiotics used.

Surprisingly, recent studies have found that chemicals such as triclosan in antibacterial soaps could be favouring resistant bacteria, by killing non-resistant bacteria and so giving the resistant individuals more access to resources like food as a result of reduced competition. The US Food and Drug Administration has now banned triclosan in soaps.

chemicals such as triclosan in antibacterial soaps could be favouring resistant bacteria

Another situation where antibiotics aren’t used correctly is with livestock. Around 80% of all antibiotics used are given to livestock. This is primarily for promoting growth (although the supporting evidence for this is inconclusive), but has lead to resistance to ‘last-resort’ antibiotics used to treat resistant infections.

Colistin is extensively given to livestock in countries such as China, promoting high levels of resistance to it, and worryingly researchers found that such resistant bacteria have leapt from pigs to humans. Colistin is used as a last-resort drug in the US, so there are worries about what we could do if the resistant strains spread globally, as bacteria don’t respect national borders.

In December, reports emerged that a woman in Nevada had been killed by a ‘superbug’ – a bacteria that had become resistant to all available antibiotics, known as pan-resistance. Said superbugs are expected to be becoming more and more prevalent in the coming years, so what can we do to tackle them?

‘A SUPERBUG (IS) a bacteria That had become resistant to all available antibiotics’

Despite the pessimistic image that the media paints of antibiotic resistance, it is not all doom and gloom. So what alternative treatments are being developed to deal with infections?

Bacteriophage therapy:

This is not a new idea – it has been considered for over 90 years, but since the healthcare revolution caused by penicillin, the Western world has largely ignored it. Research did continue in Eastern Europe and the Soviet Union, but this is inaccessible to many researchers due to language barriers.

Bacteriophage (often called ‘phage’) are viruses that naturally infect bacteria, and not animals cells. They are very abundant in nature and it is possible for us to engineer them to target specific infectious bacteria.

Ideally we would like to have about 11 different phage per bacterial pathogen. This is so we could apply them as a cocktail – by treating an infection with multiple phage, even if the bacteria becomes resistant to one, then they will still be killed anyway by another phage. This is clearly a huge advantage as the spread of resistance would be impeded.

In retrospect, this would have been a good way of using antibiotics when they were first developed, but we can now apply this knowledge to other treatments such as this.

Endolysins:

Endolysins are enzymes produced by phage to halt the cell division of bacteria. Treatment with these wouldn’t require using the whole phage, which many patients would prefer.

Scientists in the Netherlands are in the process of developing a endolysin-based treatment for eczema. Although we don’t definitively know the cause of eczema, there seems to be a correlation between having the condition and high levels of Staphylococcus aureus on your skin. The endolysins target the S. aureus, and the results are promising so far.

Introduction of predatory bacteria:

This doesn’t sound like the most inviting of treatments, but it has a lot of potential.

There are predatory bacteria, such as Bdellovibrio bacteriovorus, that don’t cause disease and survive by eating certain bacteria, many of which do cause diseases. This means we could introduce them into a patient, they will remove the pathogenic bacteria, then they are self-limiting so will die out when and our immune system kills them.

This is very exciting because there are no obvious risks to the patient, and it would be difficult for the targeted bacteria to develop resistance to the predatory bacteria.

‘we aren’t quite as hopeless as the media likes to tell us’

Metal nanoparticles:

We have known about metal nanoparticles for a number of years too. They have been added to so many products: from socks to soaps. But there are more applications within medicine which we could take advantage of.

For example, gallium nanoparticles are toxic to bacteria (but not us), and the bacteria will accidentally take them up by mistaking them for iron particles that they thought they were. In 2015, they were in clinical trials for cystic fibrosis patients with lung infections, and seemed to cause a significant improvement.

So, even though antibiotic resistance is a big issue, we aren’t quite as hopeless as the media likes to tell us we are. Resistance is not futile.