In the new study, researchers from The Massachusetts Institute of Technology (USA) and the University of Naples Federico II (Italy) found that fragments of the protein pepsinogen, an enzyme used to digest food in the stomach, can kill bacteria such as Salmonella and E. coli.
The researchers believe that by modifying these peptides to enhance their antimicrobial activity, they may be able to develop synthetic peptides that could be used as antibiotics against drug-resistant bacteria. In this study, the scientists 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. To that end, they developed a search algorithm that analyzes databases of human protein sequences in search of similarities to known antimicrobial peptides.
In a screen of nearly 2,000 human proteins, the algorithm identified about 800 with possible antimicrobial activity. 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.
Once the researchers identified those candidates, they 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. This effect was seen at both acidic pH, similar to that of the stomach, and neutral pH.
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 exact mechanism by which the peptides kill bacteria is unknown, but the researchers’ hypothesis is that their positive charges allow the peptides to bind to the negatively charged bacterial membranes and poke holes in them, a mechanism similar to that of other antimicrobial peptides.
The researchers now hope to modify these peptides to make them more effective, so that they could be potentially used as antibiotics. They are also seeking new peptides from organisms other than humans, and they plan to further investigate some of the other human peptides identified by the algorithm.