Soil bacteria can produce a wealth of new antibiotics
Soil bacteria can produce a wealth of antibiotics that are new to us, claims Gilles van Wezel, Professor of Molecular Biotechnology at the Institute of Biology Leiden. His research group has developed a method that can rapidly identify and produce these unknown compounds.
New antibiotics would come in useful, because some pathogens have become insensitive to almost all used antibiotics. Big pharmaceutical companies have abandoned or cut back antibiotic research and development, now the number of substances that can be produced under standard conditions is becoming exhausted. “This is why sleeping antibiotics from Streptomyces bacteria are so interesting,” says Van Wezel. “We can wake them by adding activating molecules to the bacterial culture. But it was tricky to classify the promising compounds that then appear.” Jacob Gubbens, also from the Institute of Biology Leiden, has developed a method that makes this possible and fast. Van Wezel and Gubbens came up with the name “proteomining” for this: mining in proteins.
Van Wezel and Gubbens assume that a bacteria that produces such a complex compound initiates a whole production process in which all sorts of enzymes (proteins) make the different steps in this process possible. The good thing about bacteria is that the genes that code for such a set of enzymes are often close in the DNA. “Imagine we have a bacteria in mind that produces a promising antibiotic,” explains Van Wezel. “We then culture it under different circumstances and determine when it produces a lot, a little or none. We then search for all proteins that appear together with the antibiotic. If we find proteins that are only active when the compound is made and whose genes are close in the DNA, we then have the DNA that contains the information on the antibiotic.”
The discovery of the so called “proteomining” puts Van Wezel and his group a step further in their research to new antibiotics. So much is known about DNA that they can recognize genes in it, know which type of enzymes they code for and what these enzymes do. They therefore gain an idea of the structure of the intended compound. Van Wezel: “This greatly accelerates the classification. We can also find clues to help increase the production of the compound. Unused antibiotics are therefore emerging, which could make it more attractive for the pharmaceutical industry to come on board.” They have therefore patented the method. Other natural substances, such as medicines for cancer or fungal infections, could also be traced with this method.