Zinc blocks protein transporter in lethal bacteria

Researchers at the Universities of Adelaide and Queensland have found that zinc can ‘starve’ one of the world’s most deadly bacteria by preventing its uptake of an essential metal. Their study has been published in the journal Nature Chemical Biology.

Streptococcus pneumoniae is responsible for more than one million deaths a year, killing children, the elderly and other vulnerable people by causing pneumonia, meningitis and other serious infectious diseases. But the researchers have found that zinc ‘jams shut’ a protein transporter in the bacteria so that it cannot take up manganese, an essential metal that Streptococcus pneumoniae needs to be able to invade and cause disease in humans.

Professor Bostjan Kobe, Professor of Structural Biology at The University of Queensland, said the bacterial transporter (PsaBCA) is “responsible for keeping the bacteria alive by scavenging one essential metal (manganese), but at the same time also makes the bacteria vulnerable to being killed by another metal (zinc)”.

The study reveals that PsaBCA uses a ‘spring-hammer’ mechanism to bind the two metals, but their difference in size causes the transporter to bind them in different ways. The smaller size of zinc means that when it binds to the transporter, the mechanism closes too tightly around the zinc, causing an essential spring in the protein to unwind too far, jamming it shut and blocking the transporter from being able to take up manganese.

“Without manganese, these bacteria can easily be cleared by the immune system,” said project leader Dr Christopher McDevitt, Research Fellow in the University of Adelaide’s Research Centre for Infectious Diseases.

“With this new information, we can start to design the next generation of antibacterial agents to target and block these essential transporters.”

The research was funded by the Australian Research Council and the National Health and Medical Research Council.

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