Zinc's secret anti-microbe powers revealed
Starving bacteria Zinc kills bacteria by starving them of the essential metal manganese, new research has found.
The research, involving Streptococcus pneumoniae, which is the bacteria that causes pneumonia, meningitis and other diseases, and kills more than one million people a year, is reported in a recent issue of Nature Chemical Biology.
"Zinc is nature's antimicrobial and it's probably how our body prevents this organism from causing disease normally," says co-author, microbial biochemist Dr Christopher McDevitt, of the University of Adelaide.
Zinc has long been known to play a role in our immune system and our ability to resist infection by the numerous bacteria that we encounter every day.
During infection by S. pneumoniae, for example, zinc levels in tissues increase and previous studies have shown that zinc actually kills bacteria, but to date no one has been able to work out exactly how this occurs.
"There's been a gap in our knowledge," says McDevitt.
McDevitt noted that a protein that transports the essential metal manganese into bacterial cells, was found to have zinc bound to it.
While some thought the presence of zinc in a manganese transporter was an accident, McDevitt wasn't so sure.
"That's when I started to explore this idea that maybe the zinc wasn't killing by getting into the cell but it was killing by blocking something else [the manganese] from getting into the cell," he says.
McDevitt and colleagues used high-resolution x-ray crystallography at the Australian Synchrotron to look at what was going on at the molecular level when zinc and manganese bound to the S. pneumoniae transporter.
It turns out that while both manganese and zinc are similar enough in size and shape to bind to the same transporter, small differences play a key role.
While manganese interacts poorly with the transporter protein allowing it to be easily displaced and enter the cell, zinc binds tightly to it and starves the bacteria of maganese.
"Once zinc is bound the transporter gets jammed shut and can never open again," says McDevitt.
The fact that the bacteria use a transporter for manganese that leaves them vulnerable to zinc presents a "chemical conundrum", says McDevitt. There is no way that the bacteria can evolve to become resistant to the anti-microbial powers of zinc.
"It's just like an Achilles heel," he says. "We've never seen this in any other biological system before."
Fortunately, says McDevitt, humans don't have the same transporter and so do not have the same Achilles heel.
This is an advantage for designing antibacterial agents that target these transporters in bacteria.
"This idea of trying to starve an organism to death is a new idea we're trying to push now," says McDevitt.
"Now we understand how the transporter interacts with zinc and manganese, we can use this knowledge to build new chemicals the mimic the jamming action of zinc."
The researchers are also interested in studying why bacteria, for example in the lungs, are sometimes able to get around the body's zinc defences.