Zinc can “starve” Streptococcus pneumoniae microbes by preventing their uptake of an essential metal.
The finding opens the way for further work to design antibacterial agents in the fight against the deadly microbes, which are responsible for more than a million deaths a year. The bacteria can kill children, the elderly, and other vulnerable people by causing pneumonia, meningitis, and other serious infectious diseases.
Project leader Christopher McDevitt, from the University of Adelaide’s Research Centre for Infectious Diseases, says the study finds that zinc “jammed shut” a protein transporter in the bacteria so it could not take up manganese.
Manganese is an essential metal that Streptococcus pneumoniae needs to invade humans.
“It’s long been known that zinc plays an important role in the body’s ability to protect against bacterial infection, but this is the first time anyone has been able to show how zinc actually blocks an essential pathway, causing the bacteria to starve,” McDevitt says.
Professor Bostjan Kobe of the School of Chemistry and Molecular Biosciences at the University of Queensland says, “We can now see, at an atomic level of detail, how this transport protein 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).”
Professor Matt Cooper from the Institute for Molecular Bioscience (IMB) says antibiotic-resistant strains of Streptococcus pneumoniae emerged more than 30 years ago, with up to 30 percent of these bacterial infections now considered multi-drug resistant.
“The Centers for Disease Control classify multi-drug resistant Streptococcus pneumoniae as a serious threat, with more than one million cases per year in the US alone,” says Cooper.
“New treatments are urgently needed and our research has provided insights into how the uptake of metal ions affects the ability of Streptococcus pneumoniae to cause disease.”
The study reveals that the bacterial transporter (PsaBCA) uses a “spring-hammer” mechanism that binds zinc and manganese in different ways because of their difference in size.
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.
McDevitt says that without manganese, the immune system could easily clear the body of these bacteria.
“For the first time, we understand how these types of transporters function,” he says.
“With this new information we can start to design the next generation of antibacterial agents to target and block these essential transporters.”
The research, funded by the Australian Research Council and the National Health and Medical Research Council, appears in Nature Chemical Biology.
Source: University of Queensland