April 19, 2014

Fighting bacteria with weapons from fungi

In order to survive, organisms produce small molecules known as ‘primary metabolites’ which help it to grow, develop and reproduce.

By S.E. Gould

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This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American

In order to survive, organisms produce small molecules known as 'primary metabolites' which help it to grow, develop and reproduce. Examples include nucleic acid used to make DNA, amino acids to make proteins, and simple sugars. Once the organism is established it will often start to produce 'secondary metabolites'. Secondary metabolites are not vital for survival but have important ecological functions, for example fighting off invaders or increasing the likelihood of sexual reproduction.

Filamentous fungi can produce a wide variety of secondary metabolites with antifungal, antibacterial or even insecticidal properties. The variety and composition of these secondary metabolites varies between and even within species leading to a huge range of diverse substances.

Interestingly many of these genes for secondary metabolites were acquired by the fungi through horizontal gene transfer - the process by which one organism shares DNA with another (as opposed to the more traditional vertical gene transfer by which parents pass DNA to their offspring). Horizontal gene transfer is very common in bacteria but thought to be rarer in organisms with a nucleus such as plants, animals and fungi.

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The genes for many of the antibacterial agents often did not evolve in the fungi, but instead were transferred across from other bacteria. Genetic analysis of the genes for synthesising beta-lactam antibiotics showed strong similarity between bacterial and fungal versions, suggesting a common ancestor. This is impressive as within the fungi the genes have to adapt to an entire new system of expression and regulation compared with the bacteria.

From a medical point of view these new antibiotics from fungi are invaluable and many have already been isolated and used to treat infections. Not only can they be used in their natural state, fungal-derived antibiotics can also be a starter for further chemical modification, creating new types of antibiotics in order to combat growing bacterial resistance. An example is Cephalosporin C - which has only mild antibiotic activity within the fungi. Following synthetic modification it was adapted to the antibiotic ceftobiprole which is currently being assessed against MRSA in clinical trials.

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Reference 1: Kück U, Bloemendal S, Teichert I (2014) Putting Fungi to Work: Harvesting a Cornucopia of Drugs, Toxins, and Antibiotics. PLoS Pathog 10(3): e1003950. doi:10.1371/journal.ppat.1003950

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