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Peptide that kills intra-hospital bacteria designed

Stemming from a human molecule known as LL-37, scientists engineered and synthesized an improved peptide (type of protein), capable of offsetting the clustering of bacteria linked with infection persistence in intra-hospital environments.

In the next 30 years, bacteria will become even more resistant to antibiotic treatments and there will not be any viable way to combat infection. One of the reasons for their fortitude is that besides being very tolerant to unfavorable conditions –such as high temperatures– they also seem to work in “gangs”, that is, several infectious microorganisms group together forming what is known as a biofilm.

Approximately between six to eight human infections are related to microorganisms in biofilm status. Furthermore, when the group in this manner their antibiotic resistance capability increases between 10 to 1,000 times, as the “outer layer” they form hinders the effectiveness of drug treatments.

Indeed the formation of biofilms in catheters, prosthesis and foley catheters is one of the main causes of intra-hospital infections. Microorganisms adhere to these films and may survive for long periods of time, which may be the reason why some hospital patients do not respond well to antibiotic treatments and therefore remain sick for much more time, prolonging their stay in hospitals and clinics, increasing health system costs.

Offsetting or inhibiting the formation of bacterial biofilms such as Staphylococcus spp. –one of the most important pathogens linked to human infections– could help to solve, in part, the issue as claimed by Universidad Nacional de Colombia (UNal) Human Genetics Master´s,  Freddy Alexander Guevara Agudelo, who engineered and synthesized a molecule with this capability.

“The easiness of Staphylococcus spp. to adhere and form biofilms contribute to the development of diseases such as bacterial endocarditis –the infection of heart valves–, cystic fibrosis –a disease impacting the lungs–, osteomyelitis –an infection of the bones or bone marrow– and periodontitis, among others,” said Guevara, whose work received an honorable mention from the UNal Faculty of Medicine Superior Council.

Laboratory designed

The project carried out in association with the Colegio Mayor de Cundinamarca University, consisted in designing four peptides stemming from a human LL-37 cathelicidin amino acid sequence, a natural forming peptide produced by immune system cells known as polymorphonuclear leukocytes, which help protect the body from infections.

UNal Department of Chemistry Professor Luz Mary Salazar said that a peptide is a small part of protein, which is also formed by amino acids, “it´s like a word: in order to get a semantic meaning it is necessary to combine the adequate letters; the same thing happens in the laboratory, where the correct amino acids need to come together to form a peptide with a specific function”, she added.

“Some molecules –proteins– are part of our natural defense system and help prevent infections. However not all the protein is necessary, therefore in this project, we focused on the really active part, responsible for the defense mechanism in order to produce a short and effective peptide which would inhibit microbial conglomeration” said Salazar.

When there is an infection, the organism looks to what is available to defend itself and one of the mechanisms it uses is releasing antimicrobial molecules, such as the LL-37 peptide chosen by the researchers. Based on this peptide and using bioinformatics tools, Guevara engineered four analog peptides: LL37-1, LL37-2, LL37-3, and LL37-4, which are distinguished by the location of the amino acids, as the purpose was to maximize the defensive performance against bacterial groups. Afterwards, he chemically synthesized them at the UNal Department of Chemistry Membrane Lab.

Peptide effectiveness

Liliana Muñoz, Colegio Mayor de Cundinamarca UniversityProfessor, says that in order to test the effect of the peptides, they were applied directly over the multi-resistant bacterial biofilms –in this specific case Staphylococcus sp.– previously isolated from second and third level hospitals.

In this manner they proved that the peptide known as LL37-1 showed the best performance, as at a low concentration (5 µM) it destroyed 90% of the biofilms. The rest of the peptides had similar results although at a greater concentration, shown by  reduced bacterial activity.

During the research project that also carried out cytotoxicity tests, in other words, the capacity of the peptide to impact human cells. “We actually tested if these peptides specifically impacted red blood cells and discovered absolutely no damage to these cells. However it is necessary to carry out additional tests in human subjects,” said Guevara, whom carried out a research internship at the University of British Columbia and also obtained a full scholarship to participate in an advanced antibiotics course at the Pasteur Institute and the Mérieux Foundation in Annecy (France).

Thanks to the results, the research team will test the peptides in fungi and other bacterial species with the purpose of contributing to improving patient health and reducing hospital stays. Likewise, LL37-1 could have applications as an ingredient in antibacterial gels to prevent the formation of biofilms or in dentist treatments for the prevention of cavities.

Consejo Editorial