Bacteria protect themselves from the environment using their cell wall. This outer shell, which consists of carbohydrates, also counters the effects of the osmotic pressure that prevails within the bacterial cell. When a bacterium divides, a special enzyme known as D-D transpeptidase ensures that the components of the cell wall are newly cross-linked. This is precisely the process targeted by penicillin, the first antibiotic to be discovered: it blocks the bacterial enzyme and thus prevents the microbes from dividing. Penicillin is produced from a mould fungus of the genus Penicillium, which can thereby protect itself from bacterial attacks. This is why the Scottish scientist Alexander Fleming was able to observe that in a bacterial culture contaminated with this fungus no bacteria grew in the proximity of the fungus.
It took another few years for this antibiotic effect to be tested on humans. Researchers in the 1940s and 1950s quickly discovered other substances formed by bacteria or fungi that inhibit the growth of other microbes or even destroy them. To the present day, antibiotics are among the most effective weapons available for fighting bacterial infections. They are one of the most important medical discoveries of modern times and have saved innumerable human lives. Antibiotics are produced synthetically or by using biotechnology.
Because they target structures that only arise in bacteria, antibiotics do not influence human metabolism. On the other hand, they are also useless against viruses, which have no metabolic system of their own. Unfortunately, doctors often prescribe antibiotics for colds, despite the fact that they are almost always caused by viruses. This inappropriate use, the premature termination of antibiotic treatment and their inconsistent consumption result in the emergence of an undesirable phenomenon: the spread of antibiotic resistance.
Bacteria can develop mechanisms for evading the effect of antibiotics. They can either alter the target of the drugs in such a way that it is no longer recognised by the antibiotic or produce molecules that enable them to render the antibiotic harmless. Moreover, bacteria can pass their newly acquired resistance mechanisms to other bacteria. The use of antibiotics for promoting growth and preventing disease in livestock breeding is also debated by experts as a cause of the increasing spread of antibiotic resistance.
Even the most minor bacterial infections can become dangerous as a result of antibiotic resistance. Multi-resistant bacterial strains, against which a number of different antibiotics are powerless, are spreading. According to the World Health Organisation, in the European Union, Iceland and Norway alone, every year 25,000 people die of bacterial infections that can no longer be treated using antibiotics. The European Centre for Disease Prevention and Control estimates that the financial damage suffered indirectly by the European Union due to antibiotic resistance amounts to 1.5 billion euros. Without antibiotics, not only would it be difficult to treat bacterial infections, organ transplants, chemotherapy and surgical interventions would also have far lower success rates. To prevent us from backsliding to an era similar to that which existed before the discovery of antibiotics, scientists are searching for new classes of antibiotics.
Drug discovery is a topic of particular importance at the HZI. Several of the centre’s research groups dedicate their work to different aspects of this task. Some working groups use automated test processes to search through libraries containing thousands of substances for compounds that could be of interest from a therapeutic point of view. Others focus on bacterial groups, like myxobacteria and actinomycetes, which have already been identified as promising sources of active substances. However, the microbiologists, biotechnologists, pharmacists and natural products chemists at the HZI are also interested in organisms that have not yet been extensively studied. Using nature as a model, some scientists recreate antibiotics chemically to decode their mechanisms of action and to further optimise them.
(Dr Birgit Manno)
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