Antibiotic resistance – your new worst enemy?

I’ve got some bad news for you. Something bad is coming. Something really, really, really bad… and it’s coming for you. It’s coming for me, for your friends and family. In fact, it’s coming for everyone on this planet. I’m talking about antimicrobial resistance and it’s going to make us all suffer.

Let’s back it up. What exactly is antimicrobial resistance? First, I think it’s important to go over what’s meant when we say things like microbe and antimicrobial. Right now, you’re surrounded by microbes, microscopic organisms that can include bacteria, fungi and viruses. They’re everywhere – on your skin, on that book you’re reading, on that packet of crisps you’re tearing into. They even live inside of you as part of your microbiota. Don’t worry, most of them aren’t normally a danger to us… actually, we owe our survival to them! Microbes help us to digest our food, they break down dangerous greenhouse gases in the atmosphere and purify water in waste treatment plants. By growing, or colonising on us they’re able to stop other, more dangerous organisms from taking over, they can help to boost our immune system and provide lifesaving medicine. Enjoy a cold pint of beer, a cup of coffee or a bar of chocolate? You have microbes to thank for those.

800px-e_coli_at_10000x_original
A cluster of E. coli bacterial cells at 10,000 times magnification. Image credit: Wikipedia

But not all microbes are so friendly. Some, like Staphylococcus aureus and Pseudomonas aeruginosa, can infect us, plants and animals and cause serious diseases. Normally, our immune system is pretty good at taking care of these would-be-attackers. For example, we have macrophages – big, chunky cells which can essentially swallow and break up things that seem out of place through the process of phagocytosis. Another example of our body protecting us against dangerous microbes are by T-helper cells which can release cytokines to signal other cells and determine the course of defence. But sometimes, our immune system isn’t quite enough to protect us and that’s when we need help.

Antimicrobials are molecules which can directly affect microbes, either through stopping their growth or by outright killing them. Typically, when antimicrobials are referred to, people really mean antibiotics. They’re basically the same thing, the only difference is the scope of their action – antimicrobials can deal with several types of microbe whether they’re bacteria, virus, fungus or parasite. Antibiotics on the other hand are only effective against bacteria. Antibiotics can be man-made (synthetic) or we can get them from nature – things you probably have lying around in your kitchen, like honey and cabbage, have shown antibacterial qualities. We’ve even been able to make antibiotics by using microbes themselves – it’s a dog-eat-dog world for them, and in order to protect their ‘turf’ and ensure they’re the only ones that can colonise that area, they’re able to produce poisonous chemicals that can kill other microbes. Penicillin for example, one of the granddaddies of all antibiotics, is obtained from a fungus called Penicillium chrysogenum. The incorporation of antibiotics into healthcare revolutionised the world of medicine. Had an infection? No problem, you just had to take an antibiotic like your doctor prescribed and wait for it to do its magic. Needed surgery, where your body would be exposed to all sorts of nasty bacteria just waiting to get in there and have some fun? Easy – antimicrobials would be there to protect you and save the day.

Okay, so if antibiotics are that great, what’s the big fuss? Unfortunately for us, that’s where antibiotic resistance comes in. As you might guess from the name, this is when a bacteria stops being affected by an antibiotic – it becomes resistant. Bacteria, the hardened survivors that they are, have been known to shown a natural, intrinsic resistance to certain antimicrobials, through a range of different mechanisms. They can use ATP pumps to shoot out any antibiotic which has entered the cell. They can camouflage the target that the antibiotic is aiming for by changing its structure, or they can alter the permeability of the cell to make it much harder for the drug to get in. Alternatively, the bacteria can go all out and destroy the antibiotic itself – often this is accomplished through enzymes which can attach to the antibiotic’s structure and break it up.
So a bacteria shows intrinsic resistance to a particular antibiotic – no big deal, right? All you’d need to do is use one that it doesn’t have natural immunity to – and that’s exactly what we normally do. Except… bacteria are tough little guys who haven’t survived for millions of years without a few tricks up their sleeve. That’s where the other kind of resistance comes in – acquired resistance. This means that the bacteria wasn’t always resistant to an antibiotic. Instead, it gained the ability through a genetic mutation which by chance gave it a resistance-granting trait, or it picked up a gene that which gave it resistance.

Bacteria excel at getting their hands on these resistance genes from other sources, in what’s called horizontal gene transfer. One way is by being given it from another bacteria which already has the resistance gene, through conjugation – basically the bacterial version of sex. Another way is transduction, involving bacteriophages (viruses that target bacterial cells to infect as part of their life cycle). To survive, bacteriophages inject their genetic information into bacteria and hijack it to make several copies of itself. During this process, segments of the bacterial genome can become incorporated into the virion’s – so when the copies burst out of the cell and infect another, it’s possible that a resistance gene could be passed on to the new host. Otherwise, bacteria can pick up resistance genes from free-floating DNA in their environment through transformation.

 

conjugation-essgen
Representation of bacterial conjugation. Image credit: Nature

The part that comes next is where the bad news for us really starts. Once a bacteria gets access to that resistance gene and successfully incorporates it into its own genome, it has a massive advantage over its other bacterial buddies which don’t benefit from the same antibiotic immunity – and survival of the fittest applies to bacteria just as much as it does to animals. So now, when an antibiotic is applied to the bacterial colony where one has a resistance, it’s going to survive and pass that resistance gene down to its offspring (progeny), who will then pass it on to their progeny, and so on until what we have to deal with is a veritable army of resistant bacteria. When that happens, if we still want to treat infections caused by that bacteria then its back to the drawing board to find a new antibiotic.

Starting to sound serious, isn’t it? There’s worse. In today’s society, antibiotic consumption is at an all-time high with as much as a 36% increase in their use between 2000 – 2010. Overuse of antibiotics has been shown to encourage the development of antibiotic resistance, by applying a selection pressure. Essentially, this creates a situation where bacteria which are immune to an antibiotic are able to quickly outgrow those that aren’t – so the population of these resistant bacteria skyrockets, increasing the likelihood of being infected by one of these difficult-to-treat organisms. Antibiotics are also being pumped into the livestock business with more than half of the antibiotics in use also being applied to animals, often in food to encourage their growth. China alone used approximately 63,000 tonnes of antibiotics in livestock during 2010, a figure which is likely to go up to about 105,000 tonnes by 2030. Resistant bacteria can then build up in these animals and spread to humans in multiple ways, such as through food.

It doesn’t end there. Another way resistance rates can shoot up is through the misuse of antibiotics and that’s something else we’ve been busy doing too. Over-the-counter availability of antibiotics, aside from driving the overuse of antibiotics, also lets members of the public take these drugs with no prescription and no guidance whether it’s the right choice. Ever had a cold and taken antibiotics to feel better? Bad move, they aren’t going to help you – colds are caused by viruses, so antibiotics won’t help. The only thing this does is open up the possibility for even more resistance to emerge. Antibiotics don’t discriminate between the ‘bad’ bacteria and those which make up your microbiota, such as in your gut. So all that would happen is that you pointlessly kill these friendly bacteria, making room for more dangerous bacteria to settle in and upping the chance that one of these previously harmless bacteria will develop a resistance gene – which could then be passed along to something much nastier through horizontal gene transfer. And it’s not just the public that are guilty for this, with it being disturbingly common for doctors to prescribe antibiotics incorrectly or just to keep the patient happy. Compliance is also an issue, with many people not taking antibiotics for the full course and again raising the chance for a bacteria to gain resistances which make them less treatable and much more dangerous.

pills-10-390x285-262x174
Misusing antibiotics is one of the main driving forces of resistance – use them correctly! Image credit: BioSpectrum

But what does it all mean? Do we really need to make the situation sound so doom and gloom? In a word, yes. Imagine a world where even a cut could cause your death. Where simple surgery could be life-threatening and where any therapy which suppresses patient immune systems, like chemotherapy, would place the patient in huge danger. Imagine a world where each year, 10 million people die because of untreatable infections and where our average life expectancy plunges. It’s a future we’re on a direct track for.

Dame Sally Davies, the Chief Medical Officer of the NHS, described antibiotic resistance as a threat ranking alongside terrorism. The World Health Organisation (WHO) said in a report that ‘A post antibiotic era – in which common infection and minor injuries can kill – is a very real possibility for the 21st century’.

We don’t have to wait to see these effects – the consequences of increasing resistance are making themselves known right now. Multi-drug resistant bacteria, which show immunity to several antibiotics, are becoming more common, such as MRSA which kills approximately 19,000 US citizens per year and is particularly dangerous in hospital settings. We’re even starting to see bacteria that show resistance to ‘last-line’ antibiotics which are typically only reserved as a final solution, like the carbapenem class of antibiotics. The 2014 review on antimicrobial resistance made a low estimate that around 700,000 deaths are caused each year because of resistant organisms.

Relying on pharmaceutical companies to produce new antibiotics isn’t an option. The number of new classes in research and development has taken a nose dive, with only a handful of new classes produced since 2000. The way things are going, we can’t hope to keep up with the rate that resistance is rendering our antibiotics useless. Why the sudden lack in interest? The reason can mostly be attributed to money, and how much these companies could stand to make – or lose. With resistance being as common as it is, new antibiotics don’t have a particularly long lifespan before they stop doing their job, and the process of research and development can be long and expensive. So, as the companies see it, why risk investing massive amounts of money into a drug which could stop earning them money in a few years or so, when they could instead focus on much more economically safe options such as anti-cancer drugs?

So… bacteria are becoming immune to the things we’ve relied on to keep us safe for years, our antibiotic arsenal is running lower and lower, and we’re essentially around the corner from a dangerous, disease-ridden future. Is there any hope? Happily, yes. Organisations and researchers around the world are recognising how serious the situation is and are working hard to try and make sure it doesn’t happen. Alternatives to antibiotics, like phage therapy and antimicrobial peptides, are being looked into and organisations like the Research Councils UK and CDC are awarding grants to fund vital research into other new and effective ways to treat disease. Antibiotic stewardship programmes are being implemented in hospitals to ensure that these drugs are used properly and public campaigns are being launched to raise awareness.

It’s not just experts in the field who can fight the spread of resistance – the public can play a crucial part too. Simple things, like making sure you wash your hands properly and handle food in a safe, clean way can help; good hygiene means less risk of infection and less chance of needing to use antibiotics. Make sure you only use antibiotics when you absolutely have to, ensure it’s a bacterial infection and follow the course of treatment to the end! Antimicrobial resistance is something that’ll affect all of us if we don’t start trying to address the problem – but together, we can stand against it.

4 thoughts on “Antibiotic resistance – your new worst enemy?

  1. Great article; however, I would suggest that medicine must change the way antibiotics are used by ensuring at the time of diagnosis/prescription that the pathogen is sensitive to the prescribed antibiotic. That would mean that a swab for sensitivity test needs to be done at time of diagnosis. While it may be necessary to prescribe based on symptoms, in a few days results of the sensitivity test will be available and antibiotic can be changed rather than waiting for end of full course and finding out that the pathogen was resistant.

    On phage therapy the article could have pointed out that in many countries phage therapy can be made available legally under compassionate use provision and this information should be provided routinely to patients when the infection was healthcare caused or when patients are allergic to antibiotics.

    • Hi G.W Riedel, thanks for your comment! You’re right that checking the pathogen is actually susceptible to the antibiotic is a crucial step. A few weeks ago I read an interesting paper about a new device called a microfluidic cantilever which could be used to rapidly determine which bacteria is present in a sample, and which antibiotics are effective against it. I think the people who designed it are in the process of developing a handheld version which could go to market.

      Paper: http://www.nature.com/articles/ncomms12947

      • I was just reflecting on the absurdity of the statement that goes roughly like this: Lytic phages are natural products and cannot be patented and large pharmaceutical companies are not interested. On the other hand, the same thing can be said about marijuana and yet governments are now becoming leaders in making it available as a medical product and recreational product that can be produced, regulated and make money and taxes – go figure!??

  2. Both the crisis in antibiotic resistance and emerging knowledge of human microbiota suggest that we need to rethink our entire prevailing, Big Pharma-dominated, Tertiary Care-centered healthcare model. We are essentially encountering the same issues at a microecological level that we have been encountering at a macroecological level. In agriculture and other realms of human activity reliant on ecosystem services, there is increasing awareness that ecologically integral approaches are required, not merely for pest management, but for productivity, resilience, etc. I believe the same is true with respect to our internal ecosystems.

Leave a Reply

Share This
%d bloggers like this: