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Fighting bacteria with weapons from fungi

The views expressed are those of the author and are not necessarily those of Scientific American.


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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.

Microscopic image of Penicillium sp. which produces penicillin as a secondary metabolite. Credit link below.

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.

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.

Gene transfer between bacteria, archaea and eukaryotes (plants, animals and fungi). Both bacteria and archaea share lots of genes with each other, while eukaryotes only carry out vertical gene transfer while picking up the occasional gene from 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.

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

Credit link for image 1

Credit link for image 2

S.E. Gould About the Author: A biochemist with a love of microbiology, the Lab Rat enjoys exploring, reading about and writing about bacteria. Having finally managed to tear herself away from university, she now works for a small company in Cambridge where she turns data into manageable words and awesome graphs. Follow on Twitter @labratting.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. tuned 10:17 am 04/19/2014

    That’s what penicillin is, from mold.
    P.S. The bottom picture looks like a 500 KV line. Must be high power science.
    X>

    Link to this
  2. 2. Annie25 2:10 pm 04/19/2014

    (STUDENT#: 14061122)

    If antibacterial agents came from bacteria, doesn’t that imply a possibility that these agents could be produced using bacteria rather than fungi? That would be amazing because it would be faster and therefore more can be produced at a lower cost I’d imagine.

    Another thought that came into my head concerned the horizontal gene transfer. If it is possible that bacteria share their DNA with eukaryotes then, much like using viruses as vectors, our DNA could be altered to produce antibacterial agents just by a bacterium having “shared” its DNA.

    I know it isn’t as simple as this but if these are possibilities they would be quite interesting experiments to perform.

    Thank you for this.

    Link to this
  3. 3. S.E. Gould in reply to S.E. Gould 3:58 am 04/24/2014

    @Annie: Thanks so much for your comment, sorry for the late reply I’ve been away this week.

    Many antibacterial agents are produced by bacteria and are extracted for pharmaceutical purposes. However when the genes move into fungi, the fungi often modify them, producing new and exciting antibiotics. As you point out, it’s a lot quicker and cheaper to make the antibiotics in bacteria but you get a broader selection by extracting them from many different species.

    Our genes could potentially be modified to produce antibiotics but there are three problems with this. Firstly the process of gene transfer is random and very rare. It is also notoriously difficult to get new genes into human cells (there was a lot of excitement about this in the 90s which fizzled out once they started realising just how difficult it was). The second problem is that many antibiotics are dangerous for humans in large quantities and can lead to kidney or liver problems so you wouldn’t want your cells pumping them out regularly! And finally, there is the whole human bacteriome – normal and safe bacteria that live in your gut, throat and on your skin. These bacteria are often beneficial, and a broad spectrum antibiotic would be unable to tell the difference between them and a pathogen.

    I hope that helps with your thoughts, and thanks again for commenting!

    Link to this
  4. 4. MichaelAddidle 4:41 am 04/24/2014

    Hi

    I have been enjoying looking through the articles on your website.

    The concept of bacteria and fungi producing antibiotics in their “natural” form is a really important message to get over to microbiology undergraduates and also the general public. It is also important to emphasize that has almost certainly been happening for millions of years. I have written an article along the lines of this topic (http://microbiologymatters.com/wp-admin/post.php?post=1034&action=edit) on my own website http://www.microbiologymatters.com which focuses more on clinical microbiology.

    Michael Addidle

    Link to this
  5. 5. Annie25 3:32 am 04/27/2014

    Wow, thank you very much! Yes that helps a lot and is incredibly interesting. I’ll try and keep up with this topic. Thank you for the great reply!

    Link to this

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