Newly discovered “encrypting peptides” in human plasma show the properties of antibiotics

Graphical abstraction. Credit: DOI: 10.1021 / acsnano.1c04496

The increase in drug-resistant infections is one of the world’s most serious global health problems, with an estimated 10 million deaths each year by 2050. Some of the most toxic and antibiotic-resistant pathogens are the main life-threatening causes. , Infectious diseases obtained in hospitals, especially weakened immunity, are dangerous for critically ill patients. Traditional and continuous synthesis of antibiotics will not be able to keep up with the evolution of bacteria.

To avoid the ongoing process of synthesizing new targeted antibiotics Bacteria As they evolved, pen engineers have seen new natural resources for antibiotic molecules.

A Recent research About searching for encrypted peptides Antibacterial properties In human proteome, there are antibiotics that are naturally present in our own body. Leaded by a team of researchers and collaborators at the University of Pennsylvania, he is a presidential assistant professor of psychiatry, bioengineering, microbiology, chemistry and biomolecular engineering by using algorithms to identify specific sequences within the protein code. Posts in the laboratories of Cesar de la Fente and Marcelo Torres de la Fente were able to find new peptides or amino acid chains that have shown the potential to dodge harmful bacteria when cleaved.

Now, in the new study published in ACS NanoTogether with Angela Cesaro, the lead author and postdoctoral fellow in Derafente’s lab, the team identified three different antimicrobial peptides derived from proteins in human plasma and demonstrated their capabilities in a mouse model. Angela Cesaro played most of her work while earning her PhD. Under the supervision of the corresponding author, Professor Angela Archiello of the University of Naples Federico II. Collaborative research also includes the University of Utrecht in the Netherlands.

“We used an algorithmic approach to identify the cardiovascular system as a potential antimicrobial hotspot,” said de la Fuente. “Next, we scrutinized certain proteins in plasma.”

Apolipoprotein B plasma It carries lipids such as cholesterol throughout the body. However, when this protein is degraded, its peptide building block performs a completely different function.

Using their algorithm, the team isolated three peptides from apolipoprotein B and tested their ability to fend off different types of bacteria, including those that cause staphylococcal infections and pneumonia.

Each of the three peptides was able to penetrate the bacterial cell membrane, kill cells and prevent biofilm growth. In addition, when used with each other or in combination with pharmaceutical antibiotics, their antibiotic effects are significantly increased, requiring lower doses to combat infection.

The team also evaluated whether these peptides promoted Antibiotic resistance With these bacteria.

“There are many ways our immune cells and antibacterial peptides can attack and fight off. Bacterial infection“The uniqueness of the peptides we are investigating is their ability to attack the bacterial membrane. This is a structure that requires multiple genes to build and maintain. Typical antibiotics are resistant to bacteria. Because it targets only one gene or aspect of the bacterial cell that makes it relatively easy to develop, antibacterial agents that attack multiple targets at once, such as the peptides described here, interfere with bacterial resistance. It’s effective. “

“In our laboratory, resistance evolution experiments show how quickly new bacteria resistant to common antibiotics are selected, and conversely, the encrypted peptides found in plasma of this type. I was surprised to see that it didn’t lead to my choice, “says Cesarro. “This behavior may derive from a host defense mechanism that was developed in humans and evolved over time. This study opens new avenues for the discovery of antibiotics in proteins unrelated to the immune system. Open. This is very exciting at the moment. New antibiotic It is terribly necessary. “

In fact, it is the physicochemical properties of the bacterial membrane itself that allow peptides to be very successful in this battle.

“Peptides act rapidly on the membranes of invading bacteria through a variety of mechanisms,” says Torres. “In this case, bacterial membranes act as magnets that attract antibacterial peptides. Bacteria are overcome and destroyed by antibacterial peptides because the properties of these membranes are complex and cannot be easily modified to avoid peptide attraction. How to develop next-generation resistors. “

Eliminating the possibility of resistance means that these peptides can be used as antibiotics for a wide range of bacterial infections and can maintain efficiency longer than traditional antibiotics.

Finally, one peptide was designed, synthesized and used in a mouse model to increase stability for testing antibacterial function in vivo.Experiments have shown skin bacterial infections treated with synthetic peptides of natural origin Antibiotics It was identified from apolipoprotein B, which was able to eradicate infection in 4 days with a single dose.

“Blood was a clear place to look for encrypted peptides, as determined by the algorithm. These results provide a link between human plasma proteins and our innate immunity.” de la Fuente says. “We will continue to look for these peptide Beyond the blood, it provides connections to the nervous, digestive and immune systems in all other parts of the body. ”

Researchers have shown that “encrypted” peptides may be the source of natural antibiotics

For more information:
Angela Cesaro et al, a synthetic antibiotic derived from a protein-encrypted sequence from human plasma, ACS Nano (2022). DOI: 10.1021 / acsnano.1c04496

Quote: A newly discovered “encrypted peptide” in human plasma exhibits the properties of antibiotics (February 15, 2022).

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Newly discovered “encrypting peptides” in human plasma show the properties of antibiotics

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