Jamie Morton is the NZ Herald's science reporter.

The Big Read: Is the world on the brink of an antibiotic apocalypse?

Scientists are becoming increasingly worried about the threat of an antibiotic Armageddon but are Kiwis in the dark? As a week-long awareness campaign InfectedNZ kicks off, science reporter Jamie Morton talks to two leading Kiwi microbiologists.
Already, an estimated 700,000-plus people worldwide die each year due to drug-resistant infections. Photo / 123RF
Already, an estimated 700,000-plus people worldwide die each year due to drug-resistant infections. Photo / 123RF

It's dubbed the "antibiotic apocalypse", the potential point in the not-too-distant future where the bugs beat our drugs and millions die.

Across the world, scientists and clinicians are becoming increasingly worried about bacteria and other pathogens, which are evolving to resist drugs at a rate outpacing the development of new medicines.

This year health researchers were dismayed to learn of the first case of a person infected with a bacteria resistant to colistin, an old antibiotic with nasty side effects that is now used only as a last resort.

Already, an estimated 700,000-plus people worldwide die each year due to drug-resistant infections.

But the effect could be much more devastating when even today's easily-treatable diseases are found harder to combat.

In a world without antibiotics, previously treatable infections will once again become deadly, or may require amputation to stop them in their tracks.

Because antibiotics are also used to prevent infection in vulnerable people, it will also become life-threateningly risky to perform routine operations such as caesarean sections and joint replacements, and treatments like chemotherapy for cancer.

In a series of recent reports commissioned by former British Prime Minister David Cameron, economist Sir Jim O'Neill estimated that without urgent action, antimicrobial resistance would kill 10 million people a year by 2050, more than will die from cancer.

O'Neill also put an economic cost on the catastrophe, estimating that inaction would cost the world's economy $138 trillion by 2050.

Obviously, the World Health Organisation (WHO) characterises the problem as one of the biggest threats to global health today.

Its director-general, Dr Margaret Chan, called it the "end of modern medicine as we know it".

For how much longer will antibiotics hold out? Photo / 123RF
For how much longer will antibiotics hold out? Photo / 123RF

Of course, not all bugs are bad.

There are countless bacteria in and around us that serve important functions in developing our immune systems, supporting our health, digestion and generally just being a part of us.

Half of the cells in our bodies are bacterial cells.

But there are also countless pathogens which infect us and have been around for as long as we have.

The ability to be resistant to antibiotics has been around for much longer still.

Auckland University microbiologist Dr Siouxsie Wiles. Photo / File
Auckland University microbiologist Dr Siouxsie Wiles. Photo / File

Scientists say it's because of the careless ways we've used antibiotics in medicine and agriculture that these two negative traits are combining to form superbugs.

In agriculture, particularly, antibiotics have been widely used as growth promoters - to speed up the time it takes to get the meat to market - and to prevent infections, which is important when animals are factory-farmed.

Although animals develop on farms, they don't stay on them and because people can often carry antibiotic-resistant superbugs without their causing disease, such bugs easily travel from country to country.

Here in New Zealand, we may be far removed at the bottom of the world, but, like climate change, the threat won't be contained by borders, or to any one part of the planet.

"An island mentality means New Zealanders often dismiss the threat of infectious diseases as a Third World problem, or assume that modern medicine will easily solve an infection," said Auckland University microbiologist Dr Siouxsie Wiles.

The recent outbreak of campylobacter in Havelock North, which left more than 5000 people ill, should be a warning that people of all backgrounds are at risk and that infectious diseases have a broad impact across our society, Wiles said.

WHO divided the globe into six regions, showing each had at least one nation today in which half of clinical Klebsiella or Streptococcus are resistant to an antibiotic.

"Many people think of superbugs and infectious diseases as being a Third World problem, or just an issue for the poor," Wiles said.

Yet New Zealand's rates of many infectious diseases were higher than in the United States, Australia and Britain.

"Lots of people also don't know that bacteria and viruses are very different life forms," Wiles said.

"This means that anti-virals don't work on bacteria, and antibiotics don't work on viruses."

In countries where antibiotics were available without prescription, many people confused antibiotics with pain-killers and mistakenly took antibiotics for ailments such as headaches.

Another common misconception was that it was we who become resistant to antibiotics, rather than the microbes.

Wiles suspected this arose from a misunderstanding between how antibiotics work (by killing the bacteria directly) versus what happened when we are vaccinated (our immune system is primed to recognise and fight off the invader).

"But I think the biggest misconception is that people who don't take antibiotics, or who take them very rarely, won't be affected by antibiotic resistant bacteria, that the antibiotics will still work for them," she said.

"It doesn't matter if you've never had a course of antibiotics, or if you've had several, it all depends on the bacteria you get infected with."

Similarly, healthy people who have never had a course of antibiotics could still have antibiotic-resistant superbugs living happily up their noses or in their gut.

They could easily spread from person to person, or can be picked up while travelling overseas.

"We need to get real about our vulnerability and have a national conversation about how the public, health workers, policymakers and the agriculture sector can make a difference."

An agar plate showing antibiotic resistance. Photo / File
An agar plate showing antibiotic resistance. Photo / File

At the Bioluminescent Superbugs Lab she heads at Auckland University, Wiles and her team try to tease out nasty bacteria by making them glow in the dark.

"I've always been fascinated by how microbes cause disease, but never one particular microbe, so have worked on all sorts of different bacteria over my career, from food-poisoning bacteria like E. coli, to the bacteria that causes the lung disease TB," she said.

"Over the past few years I've become very interested in understanding how bacteria might be evolving out in the wild, so have had a PhD student, Hannah Read, working on how to mimic that in the lab."

In recent years, Wiles has also started an antibiotic-discovery project, funded by Cure Kids and the Maurice Wilkins Centre for Molecular Biodiscovery.

One of two Cure Kids-supported studies aims to develop a cream for treating Staphylococcus aureus skin infections, which are becoming increasingly resistant to the antibiotic in the first-line cream treatment.

"This project is going really well, with colleagues from the School of Pharmacy at the University of Auckland, we've formulated some different creams which we've found kill S. aureus," she said.

"Next we have to see if we can kill Staph present on skin."

The second project, a collaboration with Landcare Research fungi expert Dr Bevan Weir and Auckland University chemist Associate Professor Brent Copp, is screening a collection of 10,000 fungi to see if we can discover new antibiotics.

"We've screened almost 300 so far and found 39 that are able to kill S. aureus," Wiles said.

"We're now trying to make extracts from them to see if we can identify the metabolites doing the killing. Hopefully we can and they are something novel."

The research had been rewarding for her in many ways; she'd been touched by one of Cure Kids' ambassadors, a little girl living with S. aureus.

"She's just a year younger than my own daughter and connecting with her and her family and getting to know them and how this superbugs affects them has had a profound affect on me and my motivation to find new treatments."

Meanwhile, at Massey University's Albany campus, Dr Heather Hendrickson has been progressing work around how bacteria evolve, specifically what's called horizontal gene transfer.

Essentially, bacteria can exchange pieces of DNA across species boundaries, almost like passing trading cards around.

"These exchanges can be really potent, especially when these bits of DNA include genes that give the bacterial recipient resistance to antibiotics," Hendrickson said.

Massey University microbiologist Dr Heather Hendrickson. Photo / File
Massey University microbiologist Dr Heather Hendrickson. Photo / File

"Evolution in bacteria can happen rapidly because of this process."

In the past four years, she and her students have been hunting "bacteriophages", viruses which specifically infect bacteria.

"Bacteriophages are tiny protein particles that drift around in the environment until they run into their bacterial target," she said. They then inject their DNA, which takes over the cell to make many copies of the bacteriophage.

"The bacteriophages then burst the cell in order to escape and start this process again."

These intriguing organisms are found all around us, a gram of soil has more bacteriophages than the number of people on the planet, and there are even some that have adapted to live in our noses and fight bacterial pathogens when we breathe them in.

"They are also thought to be 10 times more numerous than bacteria, so if we were to try to use them as therapies, we would have a lot to choose from."

In New Zealand, there are almost certainly bacteriophages waiting to be discovered that could kill any of the superbugs that we are concerned about.

While not approved for use in human medicine, they're being investigated by companies such as kiwifruit marketer Zespri for biocontrol.

Bacteriophages are tiny proteins that specifically infect bacteria. Photo / 123RF
Bacteriophages are tiny proteins that specifically infect bacteria. Photo / 123RF

Wiles said the potential to find bug-beating fungi was just as promising.

"Because New Zealand was geographically isolated for so long, we have organisms here that are found nowhere else on Earth," she said.

"In terms of our fungi, that means we are highly likely to have a high proportion of isolates that conceivably have evolved over different evolutionary paths than fungi from other countries which have already been found to produce antibiotics."

Further, many of the fungi now being screened at Landcare Research were isolated using unusual techniques and culture media, meaning there would be a higher proportion of odd and slow-growing things which hadn't been screened before.

There were numerous other examples of Kiwi researchers digging for breakthroughs in our own backyard.

Dr Jeremy Owen, of Victoria University, was last week awarded a Rutherford Discovery Fellowship by the Royal Society of New Zealand for a study using DNA sequencing and synthetic biology to explore the biochemistry of our uncultivated microbes.

By extracting DNA directly from complex microbial communities and storing this as a library of cloned fragments, he and his research team will be able to directly access the genes that act as blueprints for producing novel chemical entities, without being limited by the need to cultivate the host bacteria.

By delivering these instruction sets to a laboratory host that is able to read and execute them, they will generate diverse collections of new, biologically active, small molecules that have the potential to be developed into medicines.

A particular focus of the research will be the discovery of new lead compounds in the fight against antibiotic-resistant superbugs.

Another new Rutherford Discovery fellow, Dr Duncan McMillan of Canterbury University, will use new methodologies to investigate the "respiratory enzymes" that support pathogen life, potentially pointing the way to novel new antibiotics.

Could science ultimately deliver drugs that could defeat bacteria?

Wiles doubts it.

The hope was instead that we could stay ahead of bacteria long enough to survive.

"As for my levels of optimism, that all depends on how much resources get thrown at the issue," she said.

"At the moment, its bugger all, especially here in New Zealand.

"We can't find treatments without governments, philanthropists, charities, the public and the pharmaceutical all digging deep into their pockets to fund vital research."

In the short-term, Hendrickson also felt it was crucial for lawmakers to regulate the use of antibiotics in agriculture.

"The New Zealand Veterinary Association has vowed to stop unnecessary use of antibiotics in animal rearing by 2030, but I fear that for individuals faced with tough choices, it is difficult to take antibiotic use seriously when you are concerned about financial losses in a competitive market," she said.

"Consumers need to let producers know that they value antibiotic-free production by asking questions about antibiotics before buying.

"If we lose antibiotics then the cheap meat of today is really costing human lives tomorrow."

New campaign launches

The new online campaign InfectedNZ, running this week, aims to boost awareness about the health, social and economic impacts of infectious diseases and antibiotic resistance across New Zealand.

The campaign will feature a series of research-driven blog posts and social media conversation.

It's being hosted by Auckland University-based centre of research excellence Te Panaha Matatini, while data used in the discussions is collated and provided by Figure.NZ, a charity devoted to getting people to use data about New Zealand.

"We decided it was time we started a national conversation about infectious diseases and what we're going to do about the looming antimicrobial Armageddon," said Wiles, who has helped organise the campaign.

"That's why we've asked leading health, social and economic researchers, and people with personal stories, to write for us this week at tepunhahamatatini.ac.nz and on social media with #infectedNZ."

- NZ Herald

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