American and Italian researchers found a new antibiotic candidate in the human body, offering a potential in developing new drug that could be used as antibiotics against drug-resistant bacteria.
A new study published on Monday in the journal ACS Synthetic Biology showed that fragments of the protein pepsinogen, an enzyme used to digest food in the stomach, could kill bacteria such as Salmonella and E. coli.
"These peptides really constitute a great template for engineering. The idea now is to use synthetic biology to modify them further and make them more potent," said Cesar de la Fuente-Nunez, a Massachusetts Institute of Technology (MIT) postdoc, and one of the senior authors of the paper.
Antimicrobial peptides, which are found in nearly all living organisms, can kill many microbes, but they are typically not powerful enough to act as antibiotic drugs on their own, according to the study.
In the new study, the researchers wanted to explore whether other proteins found in the human body, outside of the previously known antimicrobial peptides, might also be able to kill bacteria.
They developed a search algorithm that analyzes databases of human protein sequences in search of similarities to known antimicrobial peptides.
"It's a data-mining approach to very easily find peptides that were previously unexplored," said de la Fuente-Nunez.
In a screen of nearly 2,000 human proteins, the algorithm identified about 800 with possible antimicrobial activity.
Then, the research team focused on the peptide pepsinogen, whose role is to break down proteins in food.
After pepsinogen is secreted by cells that line the stomach, hydrochloric acid in the stomach mixes with pepsinogen, converting it into pepsin A, which digests proteins, and into several other small fragments, according to the study.
The researchers tested them against bacteria grown in lab dishes and found that they could kill a variety of microbes, including foodborne pathogens, such as Salmonella and E. coli, as well as others, including Pseudomonas aeruginosa, which often infects the lungs of cystic fibrosis patients.
Also, this effect was seen at both acidic pH, similar to that of the stomach, and neutral pH.
"The human stomach is attacked by many pathogenic bacteria, so it makes sense that we would have a host defense mechanism to defend ourselves from such attacks," said de la Fuente-Nunez.
The researchers also tested the three pepsinogen fragments against a Pseudomonas aeruginosa skin infection in mice, and found that the peptides significantly reduced the infections.
The researchers now hope to modify these peptides to make them more effective, so that they could be potentially used as antibiotics.