Antibiotic-resistant bacteria are poised to become a major health threat in the coming decades, but now it turns out that new antibiotics might have been inside us all along. Researchers at the University of Pennsylvania used a “search” algorithm to find dozens of potential antimicrobial peptides in the human body.
As ever-evolving bacteria develop resistance to our drugs, previously treatable infections become dangerous again – in fact, it’s predicted that these “superbugs” could cause 10 million deaths per year by 2050. With our last line of defense already beginning to fail, scientists are searching for new drugs in a variety of places, including green tea, tobacco flowers, human breast milk, rattlesnake venom, frog skin, fungi, and even platypus milk.
For the new study, researchers searched for new antimicrobial peptides (AMPs) in the human body. Like a search function for finding specific words or phrases in a document, they used an algorithm to find peptides with antimicrobial properties within the human proteome, the complete library of proteins produced in the body.
The team started by scanning the proteome for peptides with characteristics common to all AMPs – namely, a length of between eight and 50 amino acids, a positive charge, and containing both hydrophobic and hydrophilic pieces. This search returned 2,603 hits, and intriguingly they had no connection to the immune system, leading the team to refer to them as “encrypted peptides.”
The researchers then selected 55 of these peptides and tested their effectiveness against eight pathogenic bacteria, including E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Infections of these bacteria are often acquired in hospitals and can be dangerous and difficult to treat.
“We found that 63.6 percent of these 55 encrypted peptides displayed antimicrobial activity,” says César de la Fuente, lead researcher on the study. “Interestingly, these peptides not only fought off infection by some of the most harmful bacteria in the world, they also targeted gut and skin commensal organisms that are beneficial to us. We speculate that this could be indicative of a microbiota modulating role that these peptides may possess as well.”
The AMPs performed even better when grouped together with others from the same region of the body, with their antimicrobial powers boosted by 100 times. In tests in mice, the team found that the new AMPs performed as well as existing antibiotics, without causing any visible signs of toxicity.
The next set of tests examined whether these encrypted peptides would influence bacteria to develop further resistance. And the results there seem promising as well.
“What we found was that these encrypted molecules attack bacteria by permeating their outer membranes, an integral organelle for survival,” says de la Fuente. “This more damaging membrane permeation would require a great amount of energy and multiple generations of mutations to create resistance in bacteria, indicating that these newly discovered peptides are good candidates for sustainable antibiotics.”
The researchers say that not only could the study lead to new natural antibiotics to combat the rising threat of superbugs, but the technique used to find them could also help uncover hidden therapeutic molecules for other illnesses and diseases.
The research was published in the journal Nature Biomedical Engineering.
Source: University of Pennsylvania
