Discovery of how molecular ‘piracy’ works provides new strategies to combat bacterial infection

The atomic structure of the iron containing fungal molecule Coprogen in complex with the bacterial transporter. (Credit: Dr Rhys Grinter).

New research from Monash University explains the molecular mechanisms that allow bacteria to engage in ‘molecular piracy’, stealing iron atoms from their fungal competitors.

The study, led by Dr Rhys Grinter, research fellow in the School of Biological Sciences, used the Australian Synchrotron to determine the atomic detail of how bacteria use specialised molecular machines or ‘transporters’ to intercept iron-containing molecules destined for fungi.

The work illustrates, in unprecedented detail, how piracy of the essential nutrient iron occurs between rival microbes.

This phenomenon is widespread in the microscopic communities that exist all around us and inside our bodies, and is thought to play a key role in determining which species thrive in these communities.

“Microbial life is diverse, crowded and access to resources is fiercely competitive; basically, it’s a jungle down there and creative strategies are required for survival,” Dr Grinter said.

A key finding of this study is that bacteria are very selective about the atomic structure or shape of iron containing molecules they transport.

This is because in order to discourage theft, fungi spike iron-containing compounds with antibiotics that will kill the bacteria if ingested. This Trojan horse strategy has catastrophic consequences for the bacteria, as it did for the ancient city of Troy, and so bacteria go to great lengths to only import the desired cargo.

“By understanding how iron-containing molecules are recognised by the bacteria and how antibiotics are excluded, we can design new antibiotics that exploit this Trojan horse strategy to kill bacterial pathogens,” Dr Grinter said.

The potential of this aspect of the research for the development of new antibiotics is significant and important, given the looming crisis of antibiotic resistance.

Outside of iron-piracy from fungi and antibiotic development, this study is also important for fighting bacterial infection in humans.

In order to obtain iron during infection, disease causing bacteria employ the same strategy as reported in this work, by targeting iron-containing molecules in our body.

By understanding how the transporters responsible for iron-piracy function, this study paves the way for the development of strategies to inhibit bacterial iron uptake to fight bacterial infection.

“Basically, if bacteria invade our body and are unable to obtain iron, they are unable to cause infection, it’s as simple as that,” Dr Grinter said.

In an emerging research program, Dr Grinter is working to apply the outcomes from this study to develop new drugs that inhibit iron transport in the bacteria that cause meningitis and the remerging sexually transmitted disease gonorrhoea.

The full findings of this study are reported  in the International Union of Crystallography Researchers Journal, the premier journal of the union of crystallography researchers.

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