Wednesday, 4 July 2012
From antibiotics to bacon sandwiches
We are at war with an invisible enemy; the foe is bacteria. This war began in 1928 with the accidental discovery of penicillin by Alexander Fleming, though it didn’t fully kick into action until the work of Chain and Florey to purify and mass produce the chemical by 1945 (ironically a significant year another war). We now have a huge array of antibiotics to fight the bacterial enemy and yet the bacteria are still winning the war through their ability to develop resistance and continue to cause infections that are becoming harder to treat. In this blog post I want to look at a well-known resistant bacteria and how resistance emerges. I also want to look at the livestock industry, not just human use of antibiotics, as this has a major part to play in our war with resistance.
I’m sure many readers will have heard of MRSA (short for methicillin resistant Staphylococcus aureus), though not necessarily all will know what it is. S. aureus is a gram positive bacterium, meaning it takes up the gram stain used to classify bacteria. It is just one of the 500-1000 bacterial species that call us humans home and often makes up part of our skin flora (the bacteria is commonly found living on the skin of healthy people). As a slight aside, it is interesting to note that humans are in fact more bacterial than they are human with roughly ten times as many bacterial cells as human cells on, and in, the average human being, S. aureus is just one of the many bacteria that can make up part of this so called microbiome. That takes care of the SA part of MRSA, so onto the MR part. Methicillin is a drug in the penicillin class of antibiotics. This class of antibiotics are known as beta-lactams, and are/were effective against gram positive bacteria (I say ‘were’ due to the prevalence of resistance). When gram positive bacteria are produced they need to form a cell wall made of many peptidoglycan molecules cross-linked with each other (peptidoglycans are amino acids, the building blocks of proteins, linked to sugar molecules). The formation of this wall protects the bacteria from its environment so it can survive. The penicillin class of antibiotics blocks construction of the wall which causes a bacterium to swell, as water enters, and eventually burst. When first described, MRSA were a group of bacteria capable of blocking the action of methicillin, so to allow the production of a stable cell wall in the presence of the drug. MRSA are now resistant to most penicillin based antibiotics, yet the name has stuck.
MRSA is not the only bacteria which have become resistant to antibiotics, but it is constantly hitting the headlines due to its prevalence in hospitals, hence why I have used it as an example here. The question to ask now is why we have resistant bacteria in the first place; the answer lies with natural selection and evolution. Natural selection can be broadly defined as the selection of advantageous traits that promote survival of an organism. Normally I would give an example of this and then move back to my main point of bacterial antibiotic resistance; however, in my view, bacterial resistance is one of the best examples of natural selection at work. As I mentioned earlier, S. aureus is often found on the skin of healthy people without causing any issues. However, if it gets under the skin or into other areas of the body it can cause an infection (impetigo, for instance). If this happens a doctor would prescribe an antibiotic to the patient which, over time, would kill the bacteria and cure the infection. The aim of the bacteria is to survive and grow, so the presence of a killer drug is bad news. The antibiotic is a ‘selection pressure’ that forces the bacteria to evolve in order to survive. If even a single bacterium develops resistance to the antibiotic (an advantageous trait), through a mutation, it will be at a huge advantage since all the fellow, non-resistant, bacteria that are clogging up space and using up resources will be wiped out by the drug. This leaves the lone mutant bacterium with all the space and resources it needs to thrive. This resistant bacterium will rapidly multiple and form a whole new colony of bacteria that are completely unaffected by the drug; giving a resistant strain.
The use of antibiotics can lead to the development of resistant strains of bacteria; however, it is an inescapable fact that we need to treat patients who have bacterial infections. What is avoidable is the unnecessary overuse of antibiotics seen around the globe. Before the issue of antibiotic resistance came to the fore-front of medical thinking it was common for antibiotics to be used for the wrong thing, such as a cold. Most common colds are caused by rhinovirus which, needless for me to say, is a viral infection. Antibiotics are completely useless against viruses since the drugs interfere with bacterial replication; a virus replicates inside a host cell, hidden away from any effects of an antibiotic. Cases of antibiotics being used to treat common colds and other viral infections has, for the most part, stopped since it was realised that this stupid overuse was leading to resistance.
The overuse of antibiotics in humans has, to an extent, been brought under control since we now understand the risk it poses. However, the story does not stop here. At the end of the Second World War, as the antibiotic era was blooming, people began to notice that feeding antibiotics to livestock made them grow faster (we still aren’t sure why exactly). This was a fantastic finding due to the obvious shortage in quality animal feed at the time and the need for a kick-start to the agriculture and livestock industries following the war. Unfortunately, just as with humans, the use of antibiotics for farm animals promotes the emergence of resistant bacteria. These bacteria can easily cause infection within the livestock which comes with obvious economic issues, but somewhat more worryingly these bacteria could easily get into the human population and cause disease that we would struggle to treat. This fact was noticed fairly early on when the EU banned the use of antibiotics used to treat humans for use in livestock in the 70s. Even with this ban, and numerous others around the use of antibiotics to promote growth, the amount of antibiotics consumed by livestock is still double that used by humans; creating a dangerous environment for the emergence of resistant bacteria.
The overuse of antibiotics is something that needs to stop; otherwise MRSA is likely to become the least of our worries. To that end it seems the world needs to follow Denmark’s lead. Denmark is the world’s largest exporter of pork, with 90% of its produce being shipped off elsewhere. At the turn of the century the Danish pork industry decided to follow the lead of its poultry industry two years previously and agreed to stop using antibiotics for growth. Since then, the use of antibiotics has dropped by around 60%. Many argued that stopping the use of antibiotics would lead to a collapse of the industry, but since 1994 the pork production of Denmark has actually risen by 50%. So not only are they giving the world more bacon sandwiches, they are also reducing the risk of giving the world highly resistant bacteria.
We are in danger of losing our war against bacteria since resistance is emerging faster than we can discover new antibiotics. If we continue to unnecessarily overuse antibiotics and drive the evolution of resistant bacteria we are shooting ourselves in the foot. The obvious place to start the reduction of antibiotic use is in the livestock industry since, as Denmark has shown, it is not essential to have antibiotics for the industry to survive. The first step would be to stop vets making a profit from the sale of antibiotics to farmers (a blatant conflict of interest), followed by the implementation of a good surveillance system to monitor the use of the drugs. If we can curb our use of antibiotics it is likely to extend their shelf life, which will in turn buy us more time to find new and improved antibiotics or to work towards alternatives. If we continue down the path of promoting the emergence of antibiotic resistant bacteria we are in danger of heading back to a pre-antibiotic era in which what is currently a simple and treatable infection could become life threatening.