Structure determination of Garvicin KS Biochemistry/Structural biology
Antibiotics have not only saved patient lives, but been essential for all major advances in medicine and surgery achieved the last 50 years. Without antibiotics, what now is minor infections may become life threatening and advanced treatments such as transplantations, hart and cancer surgery would become difficult due to infections. World health organization (WHO) states the following: “Antibiotic resistance is one of the biggest threats to global health, food security, and development today”1, and “Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill”.2 Development of new antimicrobial drugs and food preservatives that kill and/or prevent growth of pathogenic bacteria is thus of high importance.
Antimicrobial peptides (AMPs) are emerging as a viable alternative to antibiotics attributable to their potent antimicrobial eﬀects and low propensity for resistance development, especially in chronic infected wounds. In this project proposal we suggest the structure determination of the gene-encoded ribosomally synthesized AMP Garvicin KS (Gak)3. AMPs that are ribosomally produced by bacteria are called bacteriocins. Garvicin KS consists of three peptides (GakA, GakB and GakC). GarKS has been shown to be active against methicillin sensitive and resistant strains of Staphylococcus aureus (Figure 1).3 Work is currently ongoing generating topical formulations for treatment of wound infections.4
To use and improve the performance and reduce the chance of resistance of new antimicrobial drugs their structure and function needs to be determined. Most LAB bacteriocins target sensitive cells very specifically. Subtle structural differences in bacteriocins lead to marked differences in their specificity and potency making the full structure determination of bacteriocins necessary. The student will get to determine the structure of individual peptides that constitute the bacteriocin Gak in membrane mimicking environments (Micelles, TFE:Water or Bicelles) using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy.
Per Eugen Kristiansen, Room 2124, email: email@example.com
1. WHO, Antibiotic resistance. http://www.who.int/mediacentre/factsheets/antibiotic-resistance/en/ 2016.
2. WHO, Who is first global report on antibiotic resistance reveals serious, worldwide threat to public healt. http://www.who.int/mediacentre/news/releases/2014/amr-report/en/ 2014.
3. Ovchinnikov, K. V.; Chi, H.; Mehmeti, I.; Holo, H.; Nes, I. F.; Diep, D. B., Novel Group of Leaderless Multipeptide Bacteriocins from Gram-Positive Bacteria. Appl Environ Microbiol 2016, 82 (17), 5216-24.
4. Thapa, R. K.; Winther-Larsen, H. C.; Diep, D. B.; Tønnesen, H. H., Preformulation studies on novel garvicin KS peptides for topical applications. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 2020, 151, 105333.