Australian university-led antibiotic innovation may help avoid resistance to dangerous superbugs

Researchers at at an Australian university have developed a new form of antibiotic that can be swiftly re-engineered to avoid resistance to dangerous superbugs.

The antibiotic, which was developed by PhD candidate Priscila Cardoso and major supervisor Dr Celine Valery from RMIT's School of Health and Biosciences, has a basic architecture that allows it to be generated quickly and cheaply in a lab. The antibiotic, Priscilicidin, has tiny amino acid building blocks that allow it to be tailored to combat various types of antimicrobial resistance.

With the World Health Organization calling antimicrobial resistance "one of the top ten global public health threats facing humanity", developing new antibiotics has become more urgent than ever.

Professor Charlotte Conn, one of Cardoso's PhD supervisors, said given that urgency, Priscilicidin was an exciting breakthrough for public health.

Priscilicidin is a type of antimicrobial peptide. These peptides are produced by all living organisms as the first defence against bacteria and viruses.

After reviewing the literature on antimicrobial peptide molecular engineering, the team designed and tested 20 short peptides before settling on Priscilicidin as the best candidate.

"The pharmaceutical industry tests thousands of compounds before getting a lead candidate. In our case, only 20 designs were necessary to create an entirely new family of antibiotics," Valery said.

Conn said Priscilicidin was based on a natural antibiotic peptide, which made it less likely to cause antimicrobial resistance compared to existing conventional antibiotics.

"Current natural antibiotics are expensive and difficult to make on a large scale. They also break down quickly in the body," she said

"Priscilicidin combines the advantages of small molecular design, which means it's quick and inexpensive to synthesise in a lab, with the advantages of natural antibiotics."

Priscilicidin was derived from Indolicidin, a natural antibiotic found in cows' immune systems.

The team's research, published in January 2023 in the Women in Nanoscience 2022 special issue of Frontiers in Chemistry, showed Priscilicidin was highly active against resistant microbial strains such as golden staph, E. coli bacteria and candida fungi.

Priscilicidin works by disturbing the membrane of the microbes, eventually killing the cell. "Attacking this outer layer makes it harder for the bacteria to evolve and resist treatment," said Valery.

Lab tests showed Priscilicidin had similar antimicrobial activity as Indolicidin on common bacterial and fungal infections.

The team's research shows Priscilicidin's molecules naturally self-assemble into hydrogel form, making it ideal for creating antibiotic gels and creams.

Valery said when new drugs were created, scientists needed to consider the drug's pharmaceutical formulation.

This includes the drug's form (capsule or cream, for example) and the processes involved.

Priscilicidin's natural hydrogel form meant they can bypass some of that formulation process, Valery said.

"The fact we can control the viscosity of Priscilicidin means we can contemplate many applications as different products, diversifying the types of treatments to stop antimicrobial resistance," she said.

While the team are predominantly investigating Priscilicidin for topical applications, they are not ruling out oral applications.

"In theory, you could choose all means of administration for Priscilicidin, but none of them has been tested yet," Conn said.

"We have an oral delivery technology at RMIT for protein and peptide drugs, which will allow antimicrobial peptides to be administered orally.

We are currently looking at Priscilicidin as a candidate for this test."