Natural products as antibiotics
In our final comments on natural products we highlight how they provide many of the medicines that are widely used today.
Many of these natural products come from strains of bacteria called Streptomyces, which are found in all soils and are part of the wider family of bacteria referred to as actinomycetes. To see more information about research that use these bacteria, see the links below to studies that are ongoing at the Norwich Research Park, including UEA.
Antibiotics and resistance to them
Resistance to antibiotic drugs is a current, daunting threat, as discussed in more detail here. Bacterial infections such as, gonorrhoea, salmonella, pneumonia and tuberculosis continue to put humans at risk and this risk is increasing as more and more bacteria are becoming resistant to antibiotics. “Antimicrobial resistance” is a term used to describe resistance of a microorganism, such as bacteria, viruses and fungi, to a drug that was originally effective for treating the infection. These resistant microorganisms, or “superbugs” as they have been described by the media, can withstand attack from the antimicrobial drug. Instead, the patient is left with an infection that is extremely difficult to treat, and at an increasing risk of spreading the infection to others. Microbes have adapted to become resistant to antibiotics by evolving biochemical pathways and modifying their own physiology to either break down or avoid the effect of the antibiotic drug. This evolution of resistance is a natural process that can occurs when microorganisms replicate. But bacteria can also swap resistant traits or pick up DNA that encodes for these genetic traits from the natural environment. Our abundant use and misuse of drugs is accelerating the emergence of drug-resistant bacterial strains by actively selecting for mutant individuals naturally resistant to the drug.
Biochemistry is crucial for studying how antibiotics destroy bacteria by targeting their biological processes. We now understand how the antibiotics, which you might have taken to treat an infection, work. Penicillin targets bacterial cell walls. The essential process of transcription of DNA is targeted by an antibiotic called rifampicin, which inhibits RNA polymerase, and protein synthesis can be inhibited by another antibiotic called tetracycline, which binds to and inactivates the ribosome. As we use antibiotics we may be selecting for bacterial strains with altered biochemistry and physiological processes that can survive high doses of antibiotics. Bacteria can alter structural components such as their cell walls, which are targeted by the drug. These subtle biochemical changes to the bacterial target means that the antibiotic stops working. The bacterium is resistant and it survives and multiplies. Bacteria have developed other types of resistance. They produce enzymes that degrade or modify the antimicrobial drug to inactive it, or they increase the quantity of drug efflux transporters that pump antibiotics back out of the so the bacterial cell, the bacterium is protected and is able to survive and multiply.
Biochemistry has helped us know a lot about many antibiotics, and we even know the molecular structure of some of them. A couple that we have already heard about are penicillin and streptomycin. Try to see their structures using our Gallery. The structures are not loaded there, but remember from week 1 how you can search databases for structures you are interested in. (Hint: go to the Gallery of Molecules, click on the link “Search public databases”, type in “penicillin” and select “PubChem (small molecules)” and click on the “Search” button.) Repeat this for as many molecules as you are interested in. And remember, if you have access to the standard type of red-cyan glasses that are used to watch movies in 3D you will be able to see the structures in 3D.
We are also using biochemistry to study the pathways and mechanisms that provide physiological drug-resistance. Once scientists understand these pathways, new and effective antimicrobial compounds may be designed and synthesised. For example, the soil bacterium Streptomyces naturally produces a vast scope of varied antibiotics as part of its lifestyle. This bacterium is literally an antimicrobial factory and it has supplied about 50% of all-known antibiotics. Intense biochemical research is helping scientists to understand how this bacterium’s metabolic pathways generate these incredibly useful natural products. Armed with this knowledge, scientists are beginning to manipulate these pathways to produce novel antibacterials in a bid to combat the persistence of drug-resistant infections, one of the most significant threats currently facing mankind.