Last updated June 30, 2020 at 12:29 pm
A molecule found in marine sandworms might be a possible source of new generation antibiotics that kill multi-drug resistant bacteria.
Why This Matters: The next generation of antibiotics might come from unexpected sources.
Marine sandworms might not look like much, yet these unassuming creatures may an unlikely assistant in the hunt for a new class of antibiotics. Researchers from the University of Queensland have adapted a molecule produced by the sand-dwelling animal to improve its ability to kill superbugs.
UQ researcher Dr Alysha Elliott led research to assess peptides inspired by the natural antibiotics in sandworms, to see if they could kill multi-drug resistant strains of bacteria.
And while they had some success, early versions of the compounds were also toxic to human cells. However, with further development, the researchers eventually landed on a compound that killed bacteria with far fewer side effects.
Deeper: Explainer: What is a superbug?
“A Danish biotechnology company 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,” Elliott says.
Natural antibiotics in sandworms can pierce through bacteria’s extra line of defence
“Gram-negative bacteria have evolved to outsmart our current antibiotics, but natural antibiotics like the one found in sandworms can penetrate the cell membrane of bacteria.”
Elliott says Gram-negative bacteria were more difficult to kill due to an additional line of defence in their membranes. An outer layer of their membrane – which gram-positive bacteria lack – acts as an impermeable barrier that prevents some drugs and antibiotics from penetrating the cell. This provides gram-negative bacteria with a natural defence.
As well as this natural defensive layer, gram-negative bacteria can also acquire resistance through mutations to their DNA, and transfer of resistance genes from other bacteria.
“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,” says Dr Johnny Huang, who worked with Elliott on the research.
“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,” Elliott says.
“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.”