MIT engineers have developed new antimicrobial peptides, which can combat bacteria causing respiratory and other infections, based on a naturally occurring peptide produced by a South American wasp. The venom of insects such as wasps and bees is full of compounds that can kill bacteria. Unfortunately, many of these compounds are also toxic for humans, making it impossible to use them as antibiotic drugs.
However, in a study over mice, the team repurposed a toxin normally found in Polybia paulista — a South American wasp — to create variants of the peptide that are potent against bacteria but non-toxic to human cells.
They found that their strongest peptide could completely eliminate Pseudomonas aeruginosa — a strain of bacteria that causes respiratory and urinary tract infections and is resistant to most antibiotics.
“We’ve repurposed a toxic molecule into one that is a viable molecule to treat infections,” said Cesar de la Fuente-Nunez, postdoctoral researcher at MIT. “By systematically analysing the structure and function of these peptides, we’ve been able to tune their properties and activity,” Fuente-Nunez added.
The peptide, reported in the journal Nature Communications Biology, is small enough— only 12 amino acids — that the researchers believed it would be feasible to create some variants of the peptide and test them to see if they might become more potent against microbes and less harmful to humans. The team tested the peptides against seven strains of bacteria and two of fungus, making it possible to correlate their structure and physicochemical properties with their antimicrobial potency.
To measure the peptides’ toxicity, the researchers exposed them to human embryonic kidney cells grown in a lab dish. In mice infected with Pseudomonas aeruginosa, the team found that several of the peptides could reduce the infection and could eliminate it completely. “After four days, that compound can completely clear the infection, and that was quite surprising and exciting because we don’t typically see that with other experimental antimicrobials or other antibiotics that we’ve tested in the past with this particular mouse model,” Fuente-Nunez noted.