Bacteriocins

The majority of bacteria inside and outside our body are useful and vital to our well-being, however pathogenic bacteria can be harmful and cause disease. Antibiotics have been used to combat pathogenic bacteria and treat diseases, but the development of antibiotic-resistant bacteria worldwide poses challenges to these treatments. There is therefore an urgent need to develop new antimicrobial agents, such as bacteriocins, to combat antibiotic resistance. 

Our research group studies bacteriocins, which is a group of antimicrobial peptides. Many bacteria produce bacteriocins to kill other bacteria in order to compete for nutrients or habitats. Bacteriocins are fascinating in many aspects: they are very diverse in terms of structure, physicochemical properties and modes of action. Most bacteriocins destroy other bacteria by forming pores on their target cells, destroying membrane integrity and causing cell death. 

Our research portfolio covers both the basic and applied science of bacteriocins. This includes bacteriocin screening, purification, functional genetics, quorum sensing/gene regulation, receptor identification, and mode of action studies. The pathogens we focus on are methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and listeria. 

We aim to understand how bacteriocins interact with their receptors on target cells and how these interactions lead to pore formation and cell death. This knowledge is important to develop bacteriocins into safe and efficient applications, both as food preservatives and as novel drugs to fight antibiotic resistance. Our applied research includes developing bacteriocins into drugs to fight antibiotic-resistant pathogens.

Projects:

  1. AntiMast: Bacteriocins as alternatives to antibiotics for combating infections in veterinary medicine

    New infections caused by multidrug resistant bacteria are an increasing problem in both human and veterinary medicine. In agriculture, mastitis and listeriosis are painful diseases with high mortality rates, often caused by bacterial infections not efficiently treated with traditional antibiotics.

    Mastitis is usually caused by Staphylococcus aureus, and is the animal disease leading to the greatest milk production loss worldwide. Listeriosis is caused by the ingestion of low quality feed contaminated with Listeria monocytogenes, and may lead to huge economic losses due to the loss of infected animals and the retraction of contaminated feed.

    We have recently isolated new bacteriocins from probiotic bacteria, effective in combating antibiotic-resistant bacteria isolated from mastitis infections. The overall goal of the project is to develop novel antimicrobial products based on our patented bacteriocins, for effective treatment and prevention of mastitis and listeriosis in domestic animals like cows and goats. 

    For further reading, check out the following articles: 

    Reinseth, I.S., Ovchinnikov, K.V., Tønnesen, H.H., Carlsen, H., Diep D.B.  The increasing issue of vancomycin-resistant Enterococci and the bacteriocin solution. (2019). Probiotics Antimicrob Proteins, Online ahead of print. doi: 10.1007/s12602-019-09618-6

    Telke A.A., Ovchinnikov, K.V., Vuoristo, K.S., Mathiesen, G., Thorstensen, T., Diep D.B. Over 2000-fold increased production of the leaderless bacteriocin Garvicin KS by increasing gene dose and optimization of culture conditions. (2019). Front Microbiol, 10: 389. doi: 10.3389/fmicb.2019.00389

    Ovchinnikov, K.V., Kristiansen, P.E., Straume, D., Jensen, M.S., Aleksandrzak-Piekarczyk, T., Nes, I.F., Diep, D.B. (2017). The leaderless bacteriocin Enterocin K1 is highly potent against Enterococcus faecium: a study on structure, target spectrum and receptor. Front Microbiol, 8: 774. doi: 10.3389/fmicb.2017.00774

  2. Bacteriocins to fight against secondary infections in connection with leprosy and diabetes

    Many skin infections are caused by bacterial pathogens, and treating these infections has become challenging due to antibiotic resistance. This is true for people with leprosy or diabetes who often have severe chronic and recurrent infections in the lower limbs.

    Common pathogens involved in skin infections in these groups of patients are the bacteria Staphylococcus aureus and Pseudomonas aeruginosa. These are amongst the most frequent antibiotic-resistant pathogens, leaving common antibiotic treatments ineffective. 

    We have been working on a group of bacteriocins with very potent activity against many Gram-positive and Gram-negative pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. Our aim is to develop bacteriocins into drugs for medical use, with special focus on treatments of secondary infections in leprosy patients and in patients with diabetic wounds.

    For further reading, check out the following articles:

    Thapa, R.K., Winther-Larsen, H.C., Diep, D.B., Tønnesen, H.H. (2020). Preformulation studies on novel garvicin KS peptides for topical applications. Eur J Pharm Sci, 5: 105333. doi: 10.1016/j.ejps.2020.105333

    Thapa, R.K., Diep, D.B., Tønnesen, H.H. (2020). Topical antimicrobial peptide formulations for wound healing: current developments and future prospects. Acta Biomater, 103: 52–67. doi: 10.1016/j.actbio.2019.12.025

  3. iFermenter: Conversion of forestry sugar residual streams to antimicrobial proteins by intelligent fermentation

    Plant dry matter, so-called lignocellulosic biomass, is the largest renewable biomass feedstock on Earth. Europe produces over 14 million tons of sugar residuals from biorefineries, which could be converted to profitable products and contribute to a sustainable bioeconomy.

    Current concepts that aim to establish fermentation processes to convert residual sugar streams to high value products face challenges, including inefficient sugar utilization by microorganisms and inhibitors in the residual streams, leading to low productivity and yields.

    Our project aims to recover high-value compounds from forestry sugar residuals, and to convert these residuals to antimicrobials through cost-effective fermentation processes.

Published 11. February 2020 - 15:10 - Updated 6. May 2021 - 19:08