Biological engineers discover new antibiotic candidates

A screen of human proteins reveals some with antimicrobial power.

MIT researchers have discovered that peptides normally secreted by cells that line the stomach have previously unknown antimicrobial activity
MIT researchers have discovered that peptides normally secreted by cells that line the stomach have previously unknown antimicrobial activity. Image: Ella Maru Studio

Scientists at the MIT along with University of Naples Federico II have discovered parts of the protein pepsinogen, a catalyst used to digest food in the stomach, can eliminate bacteria, for example, Salmonella and E. coli. According to scientists, modifying these peptides could increase their antimicrobial activity.

Cesar de la Fuente-Nunez, an MIT postdoc, and Areces Foundation Fellow said, “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.”

The main aim of the study to explore regardless of whether different proteins found in the human body, outside of the already known antimicrobial peptides, may likewise have the capacity to eliminate bacteria. With that in mind, they built up a search algorithm that investigates databases of human protein arrangements looking for likenesses to known antimicrobial peptides.

In a screen of almost 2,000 human proteins, the calculation distinguished around 800 with conceivable antimicrobial action. During the study, scientists mainly concentrated on the peptide pepsinogen, whose part is to separate proteins in food. After pepsinogen is discharged by cells that line the stomach, hydrochloric corrosive in the stomach blends with pepsinogen, changing over it into pepsin A, which digests proteins, and into a few other little sections.

de la Fuente-Nunez said, “It’s a data-mining approach to very easily find peptides that were previously unexplored. We have patterns that we know are associated with classical antimicrobial peptides, and the search engine goes through the database and finds patterns that look similar to what we know makes up a peptide that kills bacteria.”

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 pHs, similar to that of the stomach and neutral pH.

The analysts additionally tried the three pepsinogen sections against a Pseudomonas aeruginosa skin contamination in mice and found that the peptides fundamentally decreased the diseases. The correct instrument by which the peptides eliminate microbes is obscure, yet the scientists’ theory is that their positive charges enable the peptides to tie to the adversely charged bacterial layers and jab gaps in them, a system like that of other antimicrobial peptides.

de la Fuente-Nunez said, “We have an atlas of all these molecules, and the next step is to demonstrate whether each of them actually has antimicrobial properties and whether each of them could be developed as a new antimicrobial.”

Other MIT authors of the paper, which appears in the Jan. 20 issue of the journal ACS Synthetic Biology, are Timothy Lu, an associate professor of electrical engineering and computer science and of biological engineering, and Marcelo Der Torossian Torres, a former visiting student.