Antibiotics: How we won the battle, and why they’re winning the war.
“The most exiting phrase to hear in science, the one that heralds new discoveries, is not ‘Eureka!’ but ‘That’s funny…” – Isaac Asimov
This is certainly true for the discovery of Penicillium, as although it was only by chance that the mould had drifted onto Alexander Flemings’ culture, it was his realisation that something unusual had happened that resulted in the scientific breakthrough. He was probably not the first scientist to have encountered penicillium; he saw what many others had, however he thought what nobody else had thought.
Penicillin is a bactericidal, as it actually kills the bacteria rather than just slowing down their growth. It does this by preventing bacteria from producing a rigid cell wall, which is vital for protecting them from toxins in the surrounding environment. Other natural antibiotics include cephalothin from the mould Acremonium, which work in a similar way to penicillin, and Gentamicin from the bacteria Micromonospora which works by inhibiting protein synthesis. Gentamicin does this by binding to the bacterium’s ribosomes, and so prevents them from sequencing amino acids into proteins. Thankfully, ribosomes in bacteria have a different structure to those in humans, and so the antibiotic can prevent protein synthesis in bacteria without affecting our own ribosomes. In the past the complex structure of antibiotics has made it difficult for bacteria to recognise and tackle them, and so retained their effectiveness in nature. However their exposure has increased so much so that only twenty years after penicillin was first used commercially, antibiotic-resistant bacteria have emerged.
When antibiotics were first discovered, they completely revolutionised medicine. Yet now, our dependence on them almost goes unnoticed, as they have become engrained into our everyday life. So many times we take their ability to treat minor infections for granted, without realising the dependence modern medicine has on these ‘miracle drugs’ not only for curing disease but in enhancing the success of surgery, childbirth and cancer treatments. To put this into perspective, the United States now produces 25,000 tons of antibiotics annually, which is more than twice the weight of the Eiffel tower. Yet this is all going to change. Bacteria are evolving, much faster than we are producing new antibiotics, and infections that once succumbed to everyday antibiotics will become deadly. Even now, many require last-resort drugs with unpleasant side effects, and others have become so difficult to treat that they kill around 25,000 Europeans yearly.
The reason for this is that bacteria are able to evolve very quickly, and very effectively. Whereas mammals such as ourselves can only exchange genetic material when reproducing, bacteria can do this by transformation, transduction and conjugation throughout their life. If a family tree displays how genes are inherited in humans, then a cobweb would be a better analogy for bacteria, as they can pass genes not only onto their offspring but to other bacteria around them. And, most amazing of all, they are not limited to their own species. Furthermore, their reproduction rate is incredibly fast. Whereas we can only reproduce once a year, they can every twenty minutes.
Transduction occurs when a bacteriophage (a virus that infects bacteria) inserts its DNA into a bacterium to replicate. When this happens, the DNA of the bacteria breaks up and some of it can get incorporated into the viruses DNA. This is then injected into another bacterium when the new virus infects it, and so the DNA from the first bacterium can be incorporated into the second bacterium DNA.
Although transduction is very much a chance occurrence as a side effect of the virus infection, conjugation is a technique that has evolved specifically to benefit the bacteria and is the direct transfer of DNA from one bacterial cell to another. Within bacteria are small loops of extra DNA called plasmids, which often contain genes for antibiotic resistance. Bacteria can extend an arm-like ‘pilus’ to a nearby bacterium, and if the bacteria contains a plasmid the other doesn’t, then it can replicate the plasmid and transfer it across. The two bacteria do not have to be of the same species, nor do they need to reproduce for this to occur, and can lead to many bacterial species becoming resistant very quickly.
So it is already very clear as to how large numbers of bacteria gain genetic resistance very quickly, and these will become more numerous in the population as those bacteria without the resistance die off, giving an evolutionary advantage to those with the resistance. However, if bacteria can so easily become resistant, how does following out the full course of antibiotics help, as we are so often told to do by our doctors? Let’s compare bacteria to ourselves, and a form of medicine we have created. When exposed to a deadly virus, such as polio, our bodies are unable to develop antibodies fast enough to combat it. However if we are provided with a much weaker form of the virus, such as a dead pathogen, our body is able to recognise the antigens and so can quickly produce the necessary antibodies if we were to come across the pathogen again. In effect, we have become ‘resistant’ to that virus. Much in the same way, when we do not carry out the full course of antibiotics, they may wipe out some but not all of the bacteria, and so the surviving bacteria have been exposed to the antibiotics but not a lethal dose of them and can therefore develop resistance.
However the blame doesn’t lie so much in those individuals who don’t complete their course of antibiotics, but in the doctors who have been handing them out like ‘medicinal candy’ since the Second World War. By D-day, some 300 billion units of penicillin were available to the armed services crossing the channel. Despite saving a countless number of lives, little was known of resistance at the time, and so little care was taken when distributing this ‘wonder drug’. Moreover, due to the immediate nature of the care needed, antibiotics were a stable prescription for most casualties. It then only took 14 years after the war ended for antibiotic resistance to be scientifically documented. Even now, many antibiotics are being prescribed for symptoms and diseases that don’t respond to them, and even more worryingly, patients are being prescribed suboptimal antibiotics which greatly increase the chance of resistance developing.
The misuse of antibiotics extends well beyond human medicine. Of the 16.4 million kilograms of antibiotics produced in the United States, 80% are used for animals, mostly not for health reasons but simply to make meat cheaper. Livestock are fed a steady supply of these drugs primarily to increase weight gain, as well as to repel infections that travel fast through factory farms. Not only does this massively increase the risk of antibiotic-resistance, but any resistant bacteria that evolve will be spread throughout the surrounding environment in manure and have the potential to cause great harm to the ecosystems, as well as increasing the risk a person has of ingesting resistant bacteria by eating rare meats. Thankfully in Europe and Canada there is a ban on antibiotic use in mean animals, yet the United States are yet to follow suit.
Antibiotic resistant bacteria have been an issue since antibiotics became widely available, however in the past we’ve always been able to develop new ones to combat them again and again, yet only 2 have been approved in the US since 2009, and the number approved for market annually continues to decline. Even more worryingly, in the past 20 years nearly every major pharmaceutical company has abandoned antibiotics. Research into new antibiotics has come to a grinding halt, right when we so desperately need them. The reason for this is not scientific, but economic. Antibiotics are used short term, are rendered useless by resistance fairly quickly, and now have to be used sparingly, so there is very little profit available and therefore little incentive for pharmaceutical companies to invest in such research. This is in stark contrast to the development of highly profitable drugs for life-long illnesses that are taken regularly, such as for mental illnesses and diabetes.
Now that research into antibiotics as we know them seems futile, a new generation seems to be the only viable solution. By this, I mean antibiotics that don’t work in the same way as the old ones; they need to be evolution-proof. One possible solution for this is to develop antibiotics that prevent the bacteria from causing disease, but don’t otherwise interfere with them, thus providing no selective advantage to resistant bacteria.
– The epigenetics revolution by nessa carey – chapter 11 – pg 205
– Allies and enemies by anne maczulac – chapter 3
– new scientist article – averting apocalypse now – march 2013
– http://highered.mcgraw– hill.com/sites/9834092339/student_view0/chapter28/bacterial_conjugation.html