How a bacteria-busting spray could help solve a meaty problem

University of Otago scientists are harnessing the power of peptides – the body's own tiny protein molecules – for a spray to help the red meat industry solve headaches around bacterial contamination and spoilage.

It’s a tell-tale sign of meat past its use-by date: a sticky, slimy coating that comes with a similarly unpleasant pong.

More than just an obvious cue to throw those smelly sausages in the bin, it represents an elaborate bacterial defence system – and one that a team of University of Otago scientists are busy trying to crack.

"Biofilms" are a dense matrix of microbial cells that bacterial communities create to seal themselves off from anything – be it heat, cold or water – that might hurt them.

Once they’ve securely encased themselves upon a piece of unwrapped steak in the refrigerator, for instance, they’re free to begin breaking it down and harvesting its nutrients, leading to those classic signs of spoilage.

But biofilms aren’t always a nuisance: they happen to shelter the beneficial bacteria that live in our gut and help us to function.

Microbiologist Associate Professor Daniel Pletzer says biofilms aren’t always such a nuisance: and they happen to shelter the beneficial bacteria that live in our gut and help us to function.

“They’re simply a natural way that bacteria protect themselves, and they just become a problem when we’re dealing with those pathogens that we need to treat, ” he says.

Because biofilms are stubbornly effective at blocking traditional cleaners and antibiotics, scientists have engineered solutions like anti-biofilm coatings for surfaces.

Daniel and his colleagues at Otago’s Faculty of Biomedical Sciences are pursuing an entirely different approach, using peptides – tiny molecules that serve as the building blocks of life.

We can think of them as short, powerful chains of amino acids. While proteins are long, complex structures that do most of the heavy lifting in our cells, peptides are like their smaller, more agile cousins.

They act as messengers, telling cells and systems what to do – whether that's beating back an infection, healing a wound, or sending a signal to a specific part of the body.

“As soon as we encounter a virus, parasite or bacteria, the first thing our bodies do is produce functional peptides to fight them off,” Daniel says.

A "smart spray’" for red meat?

After discovering a wealth of insights about certain peptides, Daniel and fellow microbiologist Dr Sam Wardell pondered how they might translate their science into a practical new tool.

“It started with Sam and me having a chat about what kind of research we could do, what’s important for New Zealand, and how we could contribute to solving a problem,” Daniel says.

Sam, who has connections with major red meat co-operative Alliance Group NZ, says the country’s primary sector stood out as an obvious area that could benefit.

“So, we asked our collaborators at Alliance, what are the kinds of issues that you see day to day? And as soon as we mentioned bacteria, they pointed out problems with contamination and spoilage.”

Red meat products account for around 15 per cent of Aotearoa's total export earnings.

While less than one per cent of this is rejected annually due to spoilage or contamination, that still represents tens of millions of dollars in lost profits.

Sam notes the high stakes involved with food biosecurity: even a weakly positive test result for shiga toxin-producing E.scherichia coli (STEC) can be enough to lose access to entire markets.

“So, if we suddenly can’t export to a whole country, that’s a massive problem for a primarily exporting nation like New Zealand.”

Current industry treatment measures include washing carcasses with hot water – a typically energy-intensive practice – or using weak chemical solutions that some overseas markets don’t accept.

Daniel and Sam's proposed solution is a spray, specially designed to attack biofilm-building bacteria, that can be applied to meat within processing plants.

But first, they need to find the right peptides for the job.

In a three-year programme, recently awarded a $1m Smart Ideas grant from the Ministry of Business, Innovation and Employment, their team is exploring "host defence"’ peptides, or HDPs.

A key part of animals’ immune systems, HDPs have recently been shown to kill bacteria, including those within biofilms.

Using artificial intelligence and computational algorithms, the team has already mined the genetic data of cattle and sheep to find the most promising ones.

So far, they’ve been able to narrow their search from thousands of possibilities to around 400 candidates, which are now being synthesised for testing in the lab.

“Ten years ago, it would have taken weeks to months to get that list of peptide structures – but it can now be done overnight,” Daniel says.

The team is screening the candidates against common spoilage-causing bacteria like E. coli and Listeria, as well as "good" bacteria like Lactobacillus, which helps maintain the balance of our microbiome.

Their hope is to find a peptide, or perhaps a combination of them, that can target biofilm-forming bacteria without harming the beneficial bugs.

The researchers are also working closely with Alliance Group collaborators, who are providing guidance and will be involved with implementing the technology in plants.

Daniel says that, if the project is successful, it could also have applications that reach beyond meat production.

These might include treating farm equipment to prevent diseases like mastitis, or medical devices to reduce contamination.

And more broadly, it might aid the growing global movement to cut back on the use of chemical cleaners and broad-spectrum antibiotics, which have contributed to the rise of antibiotic-resistant ‘superbugs’ like MRSA.

The power of peptides

In a recently published study, the team demonstrated how, when combined with a specific peptide, a powerful antibiotic called colistin could tackle bacteria it normally couldn’t treat.

That raised the exciting possibility of peptides being a key to target more hard-to-kill bacteria, while helping to reduce the amount of antibiotics needed.

They’re also eager to find peptides with “immunomodulatory activity” – or those that can boost the body's own immune system to fight off infections, rather than killing the bacteria directly.

Daniel says that one of the most promising aspects of peptides is that bacteria don’t appear to develop resistance to them as quickly as they do to traditional antibiotics.

He explains how their unique power lies within their mechanism of action.

Many antimicrobial peptides work by being positively charged, which causes them to be drawn to the negatively charged cell membrane of bacteria.

The peptide molecules then cluster around the bacterial cell, causing it to effectively burst. Other peptides penetrate the cell wall and disrupt internal functions like DNA replication.

Because they have multiple targets and don't rely on the bacteria's active metabolism, resistance is much harder to develop, Daniel says.

“Antibiotics traditionally have one target in bacteria, whereas peptides don’t care whether the bacteria are active or not – they just need to be present.”

Daniel and Sam however stress they’re not claiming to have the antidote for the mounting global health crisis of antibiotic resistance.

“It’s more about learning how these peptides can be used to augment current anti-bacterials and anti-microbials.”

Ultimately, Daniel says, a core mission of his lab is to find a way to win the long game against troublesome bugs.

“We’re not promising a new drug to kill all those multi-drug-resistant pathogens that are out there – but we are really just trying to find a way to delay them.”