Scientists at RMIT have created a new class of antibiotics that can be rapidly redesigned to circumvent resistance by dangerous superbugs.
Developed by PhD candidate Priscila Cardoso and Dr. Céline Valéry, principal supervisor of the School of Health and Biosciences, this antibiotic has a simple design that can be manufactured quickly and cost-effectively in the laboratory. .
The amino acid building block of this antibiotic, named pricilicidin, is small, so it can be tailored to tackle different types of antimicrobial resistance.
With the World Health Organization calling antimicrobial resistance “one of the top 10 global public health threats facing humanity,” the need for new antibiotics is more urgent than ever.
Professor Charlotte Conn, one of Cardoso’s PhD supervisors, said priscilicidin is an exciting breakthrough for public health given the urgency.
Pricilicidin is a type of antimicrobial peptide. These peptides are produced by all organisms as a first line of defense against bacteria and viruses.
After reviewing the literature on molecular engineering of antimicrobial peptides, the team designed and tested 20 short peptides before deciding on Pricilicidin as the best candidate.
“The pharmaceutical industry typically tests thousands of compounds before they get a lead candidate. In our case, it took just 20 designs to create an entirely new family of antibiotics,” said Valéry. I’m here.
Kong said that because pricyricidin is based on natural antibiotic peptides, it is less likely to cause antimicrobial resistance compared to existing conventional antibiotics.
“Current natural antibiotics are expensive, difficult to mass-produce, and degrade rapidly in the body,” she said.
“Priciricidin combines the advantages of natural antibiotics with the advantages of small-molecule design, which means it is quick and cheap to synthesize in the laboratory.”
How does Pricilicidin work?
Pricilicidin is derived from indolicidin, a natural antibiotic found in the immune system of cattle.
The team’s study, published in January 2023 in the Women in Nanoscience 2022 special issue of Frontiers in Chemistry, showed that pricylicidin was highly active against resistant microbial strains such as Golden staph, E. coli and Candida. I was.
Pricilicidin works by disrupting the microbial membrane, ultimately killing the cell.
“Attacking this outer layer makes it harder for the bacteria to evolve and resist treatment,” Valerie said.
Laboratory tests have shown that Pricilicidin has antibacterial activity similar to Indolicidin against common bacterial and fungal infections.
A new arsenal of topical and oral antibiotics
The team’s research shows that molecules of prisilicidin spontaneously self-assemble into a hydrogel form, ideal for making antibiotic gels and creams.
Valéry said that when a new drug is created, scientists need to consider its formulation.
This includes drug forms (such as capsules and creams) and associated processes. Pricilicidin’s natural hydrogel form meant that some of its formulation processes could be bypassed, Valery said.
“The fact that we can control the viscosity of pricyricidin means we can consider it for many uses as different products, diversifying the types of treatments we can use to stop antimicrobial resistance,” she said.
The team is primarily investigating pricilicidin for topical application, but has not ruled out oral application.
“Theoretically, any route of administration of pricilicidin could be chosen, but none have been tested yet,” said Conn.
“RMIT has an oral delivery technology for protein and peptide drugs that will enable the oral administration of antimicrobial peptides. We are currently considering pricilicidin as a candidate for this trial.”
Original: Antibiotic innovations help fight superbugs
Than: Royal Melbourne Institute of Technology | Commonwealth Scientific and Industrial Research Organization
