Antibiotic resistance: A challenge for the 21st century FACTFILE Antibiotic resistance: A challenge for the 21st century 2 Factfile: Antibiotic resistance | www.microbiologysociety.org What are antibiotics? anything that inhibits or kills microbial Any substance that inhibits the growth cells including antibiotics, antifungals, Box 1. Leafcutter ants and replication of a bacterium or kills antivirals and chemicals such as it outright can be called an antibiotic. antiseptics. Antibiotics are a type of antimicrobial Most antibiotics used today are designed to target bacterial infections produced in laboratories, but they are within (or on) the body. This makes often based on compounds scientists antibiotics subtly different from the other have found in nature (Box 1). Some main kinds of antimicrobials widely used microbes, for example, produce today: substances specifically to kill other nearby bacteria in order to gain an • Antiseptics are used to sterilise advantage when competing for food, surfaces of living tissue when the water or other limited resources. risk of infection is high, such as However, some microbes only produce during surgery. antibiotics in the laboratory. • Disinfectants are non-selective antimicrobials, killing a wide range Antibiotic preparations of micro-organisms including Antibiotic preparations come in many bacteria. They are used on non- different forms, depending on where living surfaces, for example in the infection they are targeting is hospitals. located. Creams or ointments may be applied to infections on the outside of Of course, bacteria are not the only the body, while pills or liquids are used Leafcutter ants live in huge, sprawling microbes that can be harmful to us. for most infections inside the body. colonies of up to 8 million individuals. Fungi and viruses can also be a danger Here, antibiotics are absorbed into To cultivate a fungus, Leucoagaricus to humans, and they are targeted by the bloodstream or target bacteria in gongylophorus, in ‘gardens’ within antifungals and antivirals, respectively. the digestive tract itself. Injections of their colonies, the ants feed the Only substances that target bacteria antibiotics directly into the bloodstream leaves they cut to the fungus, which are called antibiotics, while the name (intravenous antibiotics) are only used in turn is the colony’s sole food antimicrobial is an umbrella term for for the most serious infections. source. Leafcutter ants thus form Definitions of some key terms sophisticated farming societies in symbiosis with the fungal cultivar. However, the ants are not the Term Definition only ones who want a bite out of L. gongylophorus. In the warm, damp Antibiotic A class of drugs used to treat bacterial infections. underground chambers within the Used to be a synonym for antibiotics. Today, substances used ant colony, the fungus is at risk of Antibacterial to disinfect non-living surfaces are known as antibacterials. being invaded by a range of harmful fungi. The ants have evolved defences Antifungal A class of drugs used to treat fungal infections. against this constant threat – among others, they grow actinomycete Antiviral A class of drugs used to treat viral infections. bacteria on their bodies which produce antibiotics that the ants An umbrella term for antibiotics and antibacterial, antifungal use to protect themselves and their Antimicrobial and antiviral substances fungus against infection. Factfile: Antibiotic resistance | www.microbiologysociety.org 3 History of antibiotics Ehrlich, a German physician, noted Alexander Fleming was a Antibiotics have been used for millennia that certain chemical dyes coloured messy man by nature who accidentally to treat infections, although until the some bacterial cells but not others5. discovered penicillin. Upon returning last century or so people did not know He concluded that, according to this from a holiday in Suffolk in 1928, the infections were caused by bacteria. principle, it must be possible to create he noticed that a fungus, Penicillium Various moulds and plant extracts were substances that can kill certain bacteria notatum, had contaminated a culture used to treat infections by some of selectively without harming other cells. plate of Staphylococcus bacteria he the earliest civilisations – the ancient In 1909, he discovered that a chemical had accidentally left uncovered. The Egyptians, for example, applied mouldy called arsphenamine was an effective fungus had created bacteria-free bread1 to infected wounds. Nevertheless, treatment for syphilis. This became the zones wherever it grew on the plate. until the 20th century, infections that we first modern antibiotic, although Ehrlich Fleming isolated and grew the mould now consider straightforward to treat himself referred to his discovery as in pure culture. He found that P. notatum – such as pneumonia and diarrhoea – ‘chemotherapy’ – the use of a chemical proved extremely effective even at that are caused by bacteria, were the to treat a disease6. The word ‘antibiotics’ very low concentrations, preventing number one cause of human death in the was first used over 30 years later by Staphylococcus growth even when developed world2,3,4. the Ukrainian-American inventor and diluted 800 times, and was less toxic It wasn’t until the late 19th century microbiologist Selman Waksman, than the disinfectants used at the that scientists began to observe who in his lifetime discovered over time. antibacterial chemicals in action. Paul 20 antibiotics. After early trials in treating human wounds, collaborations with British pharmaceutical companies ensured that the mass production of penicillin (the antibiotic chemical produced by P. notatum) was possible. Following a fire in Boston, MA, USA, in which nearly 500 people died, many survivors received skin grafts which are liable to infection by Staphylococcus7. Treatment with penicillin was hugely successful, and the US government began supporting the mass production of the drug. By D-Day in 1944, penicillin was being widely used to treat troops for infections both in the field and in hospitals throughout Europe. By the end of World War II, penicillin was nicknamed ‘the wonder drug’ and had saved many lives. Scientists in Oxford were instrumental in developing the mass production process, and Howard Florey and Ernest Chain shared the 1945 Dr Selman Waksman (left) discusses his experiments with visiting Nobel laureate Sir Alexander Fleming in 1951. Nobel Prize in Medicine with Alexander Waksman was awarded the Nobel Prize in 1952 for the discovery of streptomycin, the first antibiotic effective Fleming for their role in creating the first against tuberculosis. mass-produced antibiotic. 4 Factfile: Antibiotic resistance | www.microbiologysociety.org A Petri dish culture of the fungus Penicillium notatum growing on agar. Routine surgery would be set back by decades without antibiotics. Why are antibiotics important? caused by bacteria that have become antibiotics became widely available. The introduction of antibiotics resistant to the antibiotics previously Antibiotics are sometimes used in into medicine revolutionised the used to treat them. It is estimated that, a limited number of patients before way infectious diseases were by 2050, the global cumulative cost surgery to ensure that patients do not treated. Between 1945 and 1972, of antibiotic resistance will reach contract any infections from bacteria average human life expectancy US$100 trillion9. entering open cuts. Without this jumped by eight years, with antibiotics In the 1950s and 1960s new precaution, the risk of blood poisoning used to treat infections that were drugs were being isolated all the would become much higher, and previously likely to kill patients. time10,11. However, the rate of drug many of the more complex surgeries Today, antibiotics are one of the discovery has slowed markedly. doctors now perform may not be most common classes of drugs This lack of effective new antibiotics possible. used in medicine and make possible means that drugs previously set aside many of the complex surgeries that as ‘reserve’ antibiotics, meant to be How do antibiotics work? have become routine around the used only when no other treatment Antibiotics are used to treat world. is available, are being used more and bacterial infections. Some are highly The public health revolution more regularly – and resistance is specialised and are only effective that antibiotics brought about was developing to them, too. Some of against certain bacteria. Others, known not without its cost. The more we these reserve antibiotics are also as broad-spectrum antibiotics, attack use them, the more resistant more toxic or have more severe a wide range of bacteria, including bacteria become. The US Department side effects than more standard ones that are beneficial to us. of Health estimates that half of antibiotic treatments. There are two main ways in all antibiotics used worldwide are If we ran out of effective which antibiotics target bacteria. either unnecessary or prescribed antibiotics, modern medicine They either prevent the reproduction incorrectly8. would be set back by decades. of bacteria or they kill the bacteria, With antibiotic resistance on Relatively minor surgeries, such for example by stopping the the rise, increasing numbers of as appendectomies, could become mechanism responsible for building people die every year of infections life-threatening, as they were before their cell walls. Factfile: Antibiotic resistance | www.microbiologysociety.org