UTIs are one of the prominent bacterial infections across the globe, with about 150 million cases each year, and can lead to serious health problems like chronic kidney infection (pyelonephritis) and sepsis.
Recently in a study, it was found that zinc can play a vital role in the development of new non-antibiotic treatment strategies for UTIs using our immune system.
The study was done by the researchers, including members of the IMB (Institute for Molecular Bioscience) – Professor Matt Sweet, Dr. Ronan Kapetanovic and Claudia Stocks, and members of UQ’s School of Chemistry and Molecular Biosciences – including Professor Mark Schembri and Dr. Minh-Duy Phan, examined how our immune system uses zinc to fight against bacterial infections.
“We confirmed by direct visualization that cells in our immune system known as macrophages deploy zinc to clear bacterial infections,” said Dr. Minh Duy from UQ’s School of Chemistry and Molecular Biosciences.
“We found that, compared to non-pathogenic bacteria, UPEC can evade the zinc toxicity response of macrophages, but these bacteria also show enhanced resistance to the toxic effects of the zinc.
These findings give us clues to how our immune system battles infections, and also potential avenues to develop treatments, such as blocking UPEC’s escape from zinc to make it more sensitive to this metal.”
The team developed new systems to track and analyze the insertion of zinc in macrophages, with this work just published in Proceedings of the National Academy of Sciences USA (PNAS USA).
They found that, compared to non-pathogenic E. coli, UPEC has a two-pronged strategy to survive the body’s immune response. It can prevent the delivery of zinc by hiding within the macrophage itself.
“We knew that UPEC can escape from the normal digestion pathway of the macrophage.
Our latest results show that UPEC can also avoid the delivery of zinc by hiding in different niches in these cells,” Dr. Kapetanovic said.
“It’s now clear that UPEC’s ability to occupy these specific compartments is an important factor in allowing it to spread through the body to cause severe disease.”
But evasion isn’t UPEC’s only trick. The team also found that UPEC has an enhanced ability to resist zinc toxicity.
“When we looked at UPEC, we found that they can also resist the toxic effects of zinc better than other bacteria,” Dr. Kapetanovic said.
“Taken together, these results may provide some potential avenues to develop treatments to combat UPEC and the diseases it causes, such as UTIs and sepsis. For example, blocking UPEC’s escape from zinc to make it more sensitive to this metal could help the body fight back.”
Professor Schembri and Dr. Phan used a technology called TraDIS to identify the full suite of UPEC genes involved in zinc resistance. Some of these genes had previously been explored, but a large number of others had not been explored for their involvement in protecting against zinc pressure.
Dr. Phan said, “The TraDIS analysis had given the researchers a map of which genes they could potentially target to make them more sensitive to zinc”. The team particularly focused on a type of cell called macrophage.
“Macrophages are key immune cells in the body. They digest and destroy a variety of different pathogens, have many strategies to do this, some of which are very well known and some that we’re really only discovering now.
One such recently discovered macrophage antimicrobial response uses zinc poisoning to kill bacteria, so we investigated how macrophages deploy zinc against UPEC.” said Miss Stocks.
“In creating this tool, we’ve not just found out more about E. coli, but have also created a model to study different types of bacteria, bringing us closer to not only understanding our immune system better but also to creating therapies for a range of infectious diseases.
Macrophages deploy zinc against persistent bacteria that aren’t necessarily being cleared by normal mechanisms, for example, Mycobacterium tuberculosis, Salmonella and Streptococcus; all bacteria that can cause chronic infections,” Miss Stocks said.
The new research doesn’t just have after effects for UPEC and UTIs they cause. The team has also developed zinc sensors that could be used to study a variety of disease-causing bacteria.