A “zinc” in the armour: could metal help combat common superbug?
A new study has shown that zinc plays a key role in a hospital superbug, that doctors struggle to treat due to its resistance to antibiotics.
Acinetobacter baumannii (AB) infections can cause infections in the blood, urinary tract, and lungs or in wounds in other parts of the body and are a particular issue in hospital situations. Patients can also carry AB without presenting symptoms or becoming unwell, while the bacteria causes other people to become very sick or even to die.
Unfortunately, many AB infections are resistant to antibiotics, which makes them difficult to treat.
Now, new research, published today in Proceedings of the National Academy of Sciences (PNAS), has found that zinc plays a key role in how AB cells make their shape. This identifies it as a new target to treat infections.
Just as the discovery of antibiotics was a happy accident, Dr Carmina Micelli noticed the importance of zinc when she was investigating new drug targets by studying the function of pencillin-binding proteins (PBPs), a group of chemicals known as enzymes, which control cell shape in AB bacteria.
She said: “I was using X-ray crystallography to study PBPs, when I noticed a single zinc ion in a particular structural part of PBP2. I knew this hadn’t been discovered before.
“When zinc was removed the stability of PBP2 was reduced and resulted in loss of its function. This caused AB to change shape, in the same way that antibiotics would.”
Dr Micelli worked with researchers at Northeastern and Tufts universities in the US, to show that such cells were also more vulnerable to exposure to existing penicillin-based drugs.
“This study shows that AB cell shape appears to require zinc to function. Maintenance of cell shape is vitally important for bacterial life and the enzyme PBP2 is at the heart of this process”, added Dr Micelli.
Professor David Roper for the School of Life Sciences at Warwick said: “There are several non-antibiotic drugs that can be used to trap zinc already under analysis for use in medicine. Combining these drugs with certain penicillin-based compounds could provide a new way to deal with AB infections and combat highly resistant forms of this bacteria.
“This research is also related to similar observations in Clostridium difficile (C.diff) – a common bacterial infection causing diarrhoea – so our work could have even wider medical application.”
The study is one of the first to emerge from the University of Warwick’s Sir Howard Dalton centre, a network of academics investigating novel drugs that target resistant microbes, which launched in October 2022. The Centre is generously supported by Warwick alumnus Dr David Stirling in memory of his former PhD supervisor, Sir Howard Dalton.
Further details of the research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC), can be found here: https://www.pnas.org/doi/10.1073/pnas.2215237120
Find out more about the Sir Howard Dalton centre here https://warwick.ac.uk/fac/cross_fac/howard-dalton-centre/
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15 February 2023