You’ve got a high fever, severe cough and find it hard to breathe – all symptoms of severe pneumonia. Before antibiotics, you’d likely be dead within ten days. In fact, before we had these amazing drugs, infections caused by bacteria were the leading cause of death.
Today, take a course of antibiotics and most of time you’ll be completely fine. But just what is an antibiotic, and how does it work? And what’s all this talk about antibiotic resistance and superbugs?
An antibiotic is a compound that cures infections by killing or slowing the growth of bacteria. The word literally means “anti-life”, from the Greek “bios” meaning life. The original antibiotics were made by bacteria or fungi to prevent growth or kill other bugs in what was effectively “chemical warfare” between the species during the colonisation of our planet by microorganisms billions of years ago.
Thousands of antibiotics have been discovered over the years, but most have only been shown to kill bacteria in the laboratory. Very few have become drugs because in order to do that, an antibiotic must be selective – it must kill the bacteria while not harming the cells of the human body.
An antibiotic must also have the right properties to last long enough in the body to get to the site of the infection and kill the bacteria quickly. The first antibiotic, a blue-green pigment extract from a bacterium called Pseudomonas aeruginosa, was a compound called pyocyanase. It was used to treat infections in the 1890s, but was quite toxic.
Most antibiotic drugs today are variations of substances that were originally isolated from bacteria or fungi, such as penicillin, which was isolated from a fungal mould in 1928, or vancomycin, which came from a soil-dwelling bacteria collected in Borneo in 1953.
Some commercial antibiotics used today are still isolated from bacteria grown in large fermentation vats, while others are modified chemically by scientists to improve their activity or reduce the extent of side effects. Totally synthetic antibiotics produced by chemists have been developed in the last 40 years.
While antibiotics were “discovered” around 100 years ago, they are actually ancient – microorganisms have been producing them for billions of years. Some antibiotics were produced as defence mechanisms against other bacteria, while others started off as messenger molecules between bacteria and then evolved into killing agents to allow different species of bacteria to out-compete others.
Antibiotics work by attacking the parts that a bacterium needs to grow, survive and replicate. A number of antibiotics, such as penicillin and vancomycin, inhibit the growth of the outer casing of the bacteria, which is called a cell wall. Just like the walls of a house, without a strong cell wall, the bacteria collapses.
Bacteria have a very different type of cell wall to what we find in human cells (think a double brick insulated bungalow in cold Canberra for bacteria versus a timber Queenslander in warm Brisbane for humans). This is because in people, cells are protected by being surrounded by other cells inside our bodies, while bacteria are exposed out in the environment and need stronger cell walls.
In this analogy, antibiotics such as penicillin and vancomycin are designed to attack and destroy the bricks, but not touch timber, which means they kill bacteria but don’t harm us. This image shows how vancomycin, chemically modified to glow blue, selectively attaches to the cell wall of bacteria.
Other antibiotics (such as aminoglycosides, erethromycins and tetracyclines) work by inhibiting protein synthesis, which means the bacteria can’t function (there is no kitchen or furniture inside the house). Or they block DNA replication (metronizadole and the quinolones, such as ciprofloxacin), which stops the bacteria from reproducing or replicating (so only one house is built in the suburb).
Some of these effects are bacteriostatic – they stop the bacteria growing. This gives our body’s immune system time to kick in and clear the infection naturally.
Bacteria develop resistance to antibiotics by rapidly evolving to create ways of neutralising them, actively pumping them out of their cells, or preventing them from entering in the first place. Resistance to antibiotics is now a global problem that is increasing all the time.
Paradoxically, antibiotic resistance is also ancient. Excavations of permafrost in Canada have demonstrated that genes coding for a common type of resistance to vancomycin were present over 30,000 years ago. This is because bacteria developed most of the antibiotics we use today millennia ago, and at the same time, other bacteria were evolving ways to defend themselves and resist them.
So antibiotics are a very precious, finite natural resource that we need to take much more care of.
Resistance to antibiotics is a growing problem in treating infections, and is often due to incomplete treatments. Not taking the whole course of antibiotics leads to the survival of a small number of bacteria that can tolerate the drug.
Feeding sub-lethal doses of antibiotics to livestock as growth promoters is another potential source of resistance because it creates resistant populations of bacteria within the livestock. It also results in low levels of antibiotic contamination in the environment.
Research has shown that this leads to superbugs in animals that can then get transferred to humans via our food chain. Bacteria are very promiscuous, and are able to quickly swap genes coding for resistance between different species, in a kind of “bacterial sex”. This has led to the global spread of “superbugs”, bacteria that are resistant to many types of antibiotics, and, in some cases, all antibiotics.
In 2010, bacterial infection killed more people than cancer, based on data from the WHO’s Global Health Observatory Database. Despite this enormous human cost, most pharmaceutical companies have left the field of antibiotic drug discovery, primarily for economic reasons. They make more money with drugs people take for a long time, such as the cholesterol-lowering drug Lipitor, than an antibiotic you may only need for two weeks.
The train is heading down the tunnel, but we are still walking towards it. We may be re-entering an era where simple infections can once again be death sentences.
Matthew Cooper receives funding from the NHMRC and the Wellcome Trust for antibiotic research
Mark Blaskovich works for a research group investigating the discovery of new antibiotics at the University of Queensland. He receives funding that helps support this research from the National Health and Medical Research Council of Australia and a Wellcome Trust Seeding Drug Discovery Award.