Antimicrobial proteins/peptides in humans

Research group
Active research
Project owner
Institute of Biomedicine

Short description

Increased antibiotic resistance is a growing problem in the treatment of infections, and more treatment options are needed in the future. A peptide fragment based on an antibacterial region in lactoferrin, a protein in exocrine secretions (eg breast milk, saliva, tear secretions, and in some defense cells), exhibits both antimicrobial and anti-inflammatory activity in vitro and in vivo. Series of modified synthetic peptides based on this lactoferrin fragment have been assayed for antimicrobial activity, and the most active variants have provided "lead motifs" for further modifications. A series of such modified synthetic peptides based on one of these "lead motifs" are studied for optimal antimicrobial activity in different test systems and against different microorganisms (staphylococci, E.coli, Candida and others).

With increased use of antibiotics, (multi-) resistant bacteria are also increasing in healthcare and in society, and constitute a major global problem in the treatment of infections. New treatment therapies are needed. 
Antimicrobial peptides (AMPs), which are found in all multicellular living organisms, represent an ancient innate host defense mechanism against infections. Cationic AMPs exert their antimicrobial activity by rapid killing in contrast to conventional antibiotics, which inhibit the growth. Another characteristic of AMPs is the reduced ability to induce resistance compared to conventional antibiotics.  In addition to the antimicrobial activity, these peptides are also involved in other activities, for instance inflammatory responses, wound healing responses, and angiogenesis, which make them interesting candidates in the research and development of new drugs. Thus, development of novel antimicrobial agents derived from human AMPs could become an alternative therapeutics for treatment of infections. 

We have been working for several years with synthetic cationic peptides based on an antibacterial peptide fragment of lactoferrin, one of the dominant proteins in breast milk. These synthetic peptides exhibited both antimicrobial and anti-inflammatory activities (experimental urinary tract infection, skin infection, and intestinal inflammation).

By studying the structure-microbicidal activity relationship of the antibacterial region of the peptide fragment, new synthetic peptides have been developed. One such new peptide has shown good effect in experimental skin infections, as well as anti-inflammatory activity. This peptide has been used as a new "lead motif", and further developed with regard to increased antimicrobial activity. Studies are now in progress regarding a series of new unique peptides based on this “lead sequence” concerning their antimicrobial properties in various test systems (eg salt resistance, pH, metal ions, simulated body fluids) with both bacteria and fungi (E. coli, S. aureus, P. aeruginosa, anaerobic bacteria, Candida). Selected peptides are also being studied for anti-inflammatory properties and toxicity in in vitro systems. The ability to induce resistance will also be compared with conventional antibiotics of selected peptides.

Bacteria present in the human microbiota also produce antimicrobial agents, which help to maintain a balance between different bacterial species. Recently, an antibiotic produced by a bacterial isolate (Staphylococcus lugdunensis) from the human nostril was discovered, that had a strong bactericidal effect on S. aureus also commonly found in this area (Zipperer et al Nature 2016). Those who can produce antibiotics can more easily hold on. 

We have collected bacterial strains isolated from vaginal secretions of healthy women and women with an altered vaginal microbiota. Screening of vaginal lactobacillus isolates for growth inhibitory effect on microorganisms that can often develop resistance (S. aureus, E.coli, C. albicans) gives rise to varying inhibition patterns. Lactobacillus strains with strong inhibitory effect against any of the test strains are selected for further analyzes. They will be grown in larger quantities, and the active substance will be extracted, purified and structured by mass spectrometry and NMR.
By screening of vaginal lactobacilli, both ribosomal and non-ribosomal antimicrobial substances against species-specific microorganisms can be detected.