The humble marine sandworm may help in the hunt for a new class of antibiotics after Institute for Molecular Bioscience researchers improved a molecule in the sand-dwelling animal which kills superbugs.
Dr Alysha Elliott from IMB said the study, backed by Danish biotechnology company Adenium Biotech, assessed peptides inspired by natural antibiotics in sandworms to see if they could kill multi-drug resistant strains of bacteria.
“Adenium Biotech asked for our help to investigate a small peptide called arenicin-3 that they found in the marine sandworm Arenicola marina, which could kill Gram-negative bacteria — including strains resistant to last-resort antibiotics,” Dr Elliott said.
“Gram-negative bacteria have evolved to outsmart our current antibiotics, but natural antibiotics like the one found in the sandworm can penetrate the cell membrane of bacteria.”
Dr Elliott said Gram-negative bacteria were more difficult to kill due to an additional sophisticated line of defence in their membranes.
Dr Alysha Elliott and Dr Johnny Huang were part of the research team led by Prof. Matt Cooper that tested arenicin-3 and new compounds inspired by the marine sandworm.
“While many of the initial compounds were remarkably active in killing the bacteria, they were toxic to human cells including red blood cells and did not work well in the presence of lung surfactant,” Dr Huang said.
“This would be an issue if we wanted to treat bacterial pneumonia where the infection is found in the lung.”
The researchers kept tweaking the structure of the peptide and succeeded in developing AA139, that could kill multi-drug resistant bacteria in many models of disease, with far fewer side effects.
“Our next challenge is to get this peptide to where the infections are found,” Dr Elliott said.
“Many bacterial infections are deep-seated, requiring penetration through tissue to reach them. This is a tough challenge for a peptide antibiotic, although there remains a dire unmet medical need for new antibiotics.”
This research was published in Nature Communications and was funded by Adenium Biotech ApS and the National Health and Medical Research Council.
The Institute for Molecular Bioscience is leading the global fight to stop deadly superbugs.
