Down in Otago, researchers’ focus on microbiology fundamentals is leading New Zealand’s fight against drug resistant pathogens.
In May 2016 the UK government’s Review on Antimicrobial Resistance (AMR) published its final report, summarising the Review’s findings from two years of analysis. The conclusions, whilst welcomed by the scientific community, chimed with what leading researchers, such as the University of Otago’s Professor Greg Cook, have more or less been saying for over a decade. Namely, that AMR is already a global problem (including here in Aotearoa New Zealand) and that it will take a concerted effort with governments, scientists and pharmaceutical companies working together to solve it. In the meantime the report recommended taking steps that could help prevent the rise and spread of AMR. These, in essence, can be boiled down to the three R’s of antimicrobials: Refine, Reduce and Replace, and it is these three R’s that research in Prof Cook’s laboratory focuses on.
Refining the use of antibiotics basically means using the right drugs, to treat the right bugs, at the right time. In order to achieve that, healthcare workers need rapid diagnostic tests which will tell them whether the bug their patient has is already resistant to antibiotics, and if so, to which ones. The Cook lab is part of an international collaboration between Otago and South East Asia whereby the team is trying to establish whole genome sequencing (WGS) of the tuberculosis (TB)-causing bacterium, Mycobacterium tuberculosis, as a route to faster diagnoses. WGS allows researchers to analyse the genome of AMR bacteria, looking for genetic markers that indicate which antibiotics will work and those to which the bacterium is resistant.
The second of the three R’s, Reduce, is aimed at using fewer antibiotics to lower levels of AMR in our society and in the environment. An unfortunate Catch 22 experienced in antibiotic use is that, the more you use an antibiotic, the faster resistance will arise. Around the world there are many countries that use huge numbers of antibiotics in farming. In the Unites States alone roughly 70% of antimicrobials used each year are used on animals. Luckily for us, New Zealand is one of the lowest users of antibiotics in farming worldwide but still, there’s room for improvement.
In the dairy industry, when a cow’s udder becomes infected (know as mastitis) it’s more often than not due to a bacterial infection and treatment involves a course of antibiotics, such as penicillin. Moreover, whenever a cow is treated with antibiotics its milk can’t be used and needs to be discarded. Treatment and discarded milk cost the New Zealand dairy industry over $280 million a year. In this scenario, prevention really is better than the cure, for all of us. By joining forces with a leading animal remedy company, Deosan, as well as chemists from the University of Auckland, Prof Cook and co-lead investigator Dr Adam Heikal are heading up a team dedicated to finding new bio-active, sanitising molecules to help stop dairy herds developing mastitis in the first place, thereby reducing the farmers’ antibiotic needs.
Sanitisers for dairy cows are already widely used but the bioactive molecules they contain are also used extensively in hospitals across the country and around the world. To reduce the chances of resistance to these molecules arising on the farm, and spreading to the clinic it’s vital the new molecules, specifically for farm use, are discovered and developed. That forms one part of the final R, Replace.
The search for new antimicrobials is a never-ending one. As fast as new drugs are discovered, resistance starts to evolve. For this reason, the Cook lab invests heavily in screening large libraries of chemical compounds and natural products against problem bacteria, looking for new antimicrobial drug targets. However whole organisms, even those as small as a bacterial cell, are extremely complex. To reduce the levels of complexity, once a new antimicrobial target is identified, using either reverse genetics or a good old-fashioned experimental process of elimination, the target can be purified away from the organism and studied in greater detail. Three-dimensional structures can guide researchers to make more potent, more specific drugs. Recently, the Cook lab published the first bacterial structure of a protein long thought to be a drug target for tuberculosis treatment. The challenge now is to understand, at a molecular level, the enzyme’s inner workings and to ultimately inhibit its mode of action, leading to the design of a new antimicrobial drug.
The combination of all these research activities, as well as extensive international and industrial collaborations, help the Cook lab keep New Zealand at the forefront of antimicrobial discovery.
Check out some of the data about tuberculosis and vaccinations for whooping cough from the Figure.NZ team:
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Adam Heikal PhD is a former Research Fellow in the Department of Microbiology and Immunology, University of Otago. He continues to work in AMR and antimicrobial discovery at the School of Pharmacy, University of Oslo and remains in close collaboration with Prof Cook as co-Principal Investigator on projects related to the New Zealand Agritech sector. Follow Adam on LinkedIn.
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