The Zinc-credible Solution to Persistent Bacterial Infections

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1. Summary (Provide a short plain English summary of your work, ~150 words)

Zinc is an essential nutrient in all living organisms. It is not only required for the proper functioning of enzymes and proteins, zinc deficiency in humans result in increased susceptibility to infections. Despite being a chemically inactive metal, zinc appears to have miracle-like properties. The immune system can utilise zinc in complex ways to combat infections. Zinc can function as a signal to recruit white blood cells to infection sites. The immune cells can also withhold zinc from the invading bugs resulting in their zinc starvation and eventual death. Finally, certain immune cells can also overload the invading bugs with zinc, resulting in toxicity and their death. The antimicrobial properties of zinc make it the perfect solution especially in the age of increasing antibiotic resistance. Cheryl’s research is aimed at developing new treatments that can enhance the existing zinc killing effects from our own immune system, thereby amplifying its natural killing effects.

2. Description (Describe the benefit of your research to Queenslanders, ~500 words)

The problem:
Persistent bacterial infections are a major healthcare problem both worldwide and within Australia. Cheryl’s research focuses on middle ear infections and chronic obstructive pulmonary disease (COPD) both of which are considerable health burden due to their persistence and constant reoccurrence.

COPD – In Australia, more than 1 in 20 Australians over the age of 55 have COPD, and in 2012 alone, COPD was the 5th leading cause of death. Furthermore, almost AU$1 Billion is spent on for the diagnosis and treatment of COPD.

Middle ear infections – Reports have shown that in Australia, particularly in the Indigenous children, have the highest prevalence of middle ear infections compared to the world, with rates up to 90% in some remote communities. This can result in hearing loss, speech impediment and behavioural problems.

Why are these infections so persistent?
Persistent bacterial infections in these diseases are caused by bacteria that form thick and tight communities (biofilms). As a result, drugs and antibiotics are unable to penetrate into the layers, thereby rendering them ineffective. Occasionally, these bacterial pathogens are also antibiotic resistant which, makes the situation even worse. Furthermore, these infections are usually caused by mixed communities of bacteria and, depending on the antibiotic treatment, it usually does not eradicate the entire population.

The Solution:
Zinc, the miracle metal! Zinc has emerged as an important factor in bacterial infection control. The host innate immune cells such as neutrophils and macrophages can utilise zinc to overload the bacteria, which then result in their death (Figure 1).


In fact, the idea to utilise zinc poisoning as an antibacterial strategy is merely an amplification of the existing host zinc killing effects. Currently, zinc is used in various health supplements that claim to boost the immune system, treat common colds and improve eye, gastro-intestinal and metal health diseases. It is also used as the active ingredient in anti-dandruff shampoos and, skin and acne creams. Since zinc can be used safely in humans, Cheryl’s research will focus on developing new drugs that specifically directs the zinc towards the bacteria.

Specific benefits to Queenslanders:
Based on a study performed in 2005 on over 1,700 isolates of Streptococcus pneumoniae (one of the main causes of middle ear infections and COPD) collected from 6 states within Australia, Queensland isolates recorded not only the highest % of invasive strains that were antibiotic (Erythromycin and Clindamycin) resistant, Queensland isolates as a whole had the highest % of multi-drug resistant strains. Persistent bacterial infections are already difficult to treat even if the causative agents are antibiotic sensitive. Now, with antibiotic resistance on the rise, there is an urgent need to develop alternative therapeutics. In collaboration with Queensland clinicians at the Queensland Institute of Medical Research Berghofer Medical Research Institute (QIMR Berghofer), Cheryl hopes to be able to test out her potential zinc treatment drugs against various clinical isolates collected from Queensland hospitals.

3. Additional Details (Short biography, list of key collaborators and summary of your track-record, ~500 words)

Short biography
Cheryl-lynn was born and raised in Singapore. She came over to Brisbane in 2001 and completed a Bachelor of Environmental Science in the field of Molecular and Microbial Sciences (with Class I Honours) at the University of Queensland (UQ). She then made the switch into infectious diseases and completed her PhD with Prof. Mark Schembri studying urinary tract infections at UQ. From that point, her passion for research and discovery lead to a career as a postdoctoral research fellow at UQ in Prof. Alastair McEwan’s and Prof. Mark Walker’s laboratories. Her main focus was to study pathogenic streptococcal species and have made some fundamental discoveries involving how zinc is toxic to bacteria. Her findings have also formed part of the background data to the successful NHMRC Project Grant awarded to Prof. McEwan. In 2016, She was promoted to Research Fellow at UQ and was awarded a 4-year Garnett Passe and Rodney Williams Memorial Foundation Research Fellowship jointly at QIMR Berghofer and UQ.

Collaborators
Any advancement in Science and Technology is no doubt a collaborative effort. Cheryl’s list of key collaborators include Prof. Alastair McEwan (Biochemist, UQ), Prof. Mark Walker (Microbiologist/Genetics, UQ), Prof. James Paton & Dr Christopher McDevitt (Pneumococcal research, The University of Adelaide), Dr David Reid (Clinician, QIMR Berghofer) and, Prof. Anders Cervin (ENT Sergeon, UQ).

Track Record
To date, Cheryl has 21 publications in leading Microbiology journals. She has been invited to speak at 2 local seminars and also presented 10 poster and 2 oral presentations at 9 national and 3 international conferences. As recognition of her work, she has been awarded best poster prizes at both BACPATH 2011, BACPATH 2013 conferences and the Centre for Metals in Biology Symposium 2014. To attend the international conferences, Cheryl has been awarded the UQ Early Career Travel Grant (2013), Ian Potter Foundation Travel Grant (2014), CASS Foundation Travel Award (2015). In 2016, she was awarded the Garnett Passe and Rodney Williams Memorial Foundation Research Fellowship. Cheryl is also an active part of a number of scientific organisations including Australian Society of Microbiology, International Society for Zinc Biology, Women in Technology, and Australasian Biometals Group.

Key publications:
Ong., C. Y., Gillen, C. M., Barnett, T. C., Walker, M. J., McEwan, A. G. (2014). An antimicrobial role for zinc in innate immune defense against Group A Streptococcus. The Journal of Infectious Diseases 209, 1500-1508.
 
Ong, C. Y., Walker, M. J., McEwan, A. G. (2015). Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes. Scientific Reports 5, 10799.
 
 *Djoko, K. Y., *Ong, C. Y., Walker, M. J., McEwan, A. G. (2015). Copper and zinc toxicity and its role in innate immune defense against bacterial pathogens. Journal of Biological Chemistry 290, 18954-18961. *Co-first author
 
Eijkelkamp, B. A., Morey, J. R., Ween, M. P., Ong, C. Y., McEwan, A. G., Paton, J. C., McDevitt, C. A. (2014). Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae PLoS ONE, e89427.
 

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Dr Cheryl-lynn Ong is a Research Fellow at the University of Queensland. She works primarily under the supervision and mentorship of Prof. Alastair McEwan, and also collaborates and is mentored by ...