Antibacterial Peptides and Bacteriocins
Anti-microbial/bacterial peptides (AMPs) are widely distributed in nature; they are produced by bacteria, plants and a wide variety of animals - both invertebrates and vertebrates. For animals and plants, AMPs are an important defence against microorganisms. AMPs may also for bacteria be thought of as a type of defence, since AMPs enable killing of invading bacteria that compete with the AMP-producer for nutrients.
There has especially been great interest in structure-function analysis of AMPs (often termed bacteriocins) produced by lactic acid bacteria (LAB). These AMPs (bacteriocins) are extremely potent, being active at pico to nano-molar concentrations. Moreover, the bacteria (i.e. LAB) that produce these AMPs are of “food grade quality” and industrial importance. LAB are used in food and feed production, they are part of the natural microbial flora in food humans have consumed for centuries, and they constitute a significant part of the indigenous flora of mammals, including humans. LAB and LAB AMPs/bacteriocins may, consequently, be considered to be relatively safe agents for preventing growth of pathogenic/undesirable micro-organisms. Some LAB AMPs/bacteriocins are in fact presently used as food preservatives, and the potential of LAB AMPs/bacteriocins in medical applications is exemplified by results showing that oral intake of bacteriocin-producing LAB protects mice against lethal doses of Listeria monocytogenes
About the group
The Peptide Group is involved in research on antimicrobial peptides (AMPs) produced by lactic acid bacteria (LAB). These peptides (often referred to as bacteriocins) are of great interest because they are produced by “food grade” bacteria and might consequently be utilized as relatively safe agents for preventing growth of pathogenic/undesirable microorganisms. The development of AMPs/bacteriocins into new antimicrobial agents is clearly of considerable importance in view of the dramatic increase in antibiotic-resistant pathogenic bacteria and the undesirable side effects that many chemical preservatives may have. Bacteriocins exert their antimicrobial activity in a different manner than antibiotics and preservatives, and may therefore be able to complement or possibly substitute antibiotics and preservatives.
Optimal and rational exploitation of AMPs/bacteriocins as antimicrobial agents requires insight into how AMPs/bacteriocins function at a molecular level, and this in turn necessitates insight into their three-dimensional structures. Our research focus has thus in recent years especially been on elucidating the mode-of-action and three-dimensional structure of antimicrobial peptides (AMPs) that group members have previously isolated, sequenced and genetically characterized. The research also involves elucidating the structure and mode-of-action of immunity proteins, proteins that protect bacteria from being killed by bacteriocins.
Some of the AMPs/bacteriocins have been shown to kill bacteria by a receptor-mediated mechanism, which entails that the peptides bind to specific membrane proteins, and thereby cause membrane-leakage and cell death. Through this receptor-mediated mode-of-action, the peptides show antibacterial activity at pico-molar to nano-molar concentrations.
The structure and structure-function relationships of the AMPs/bacteriocins have been analysed using NMR-spectroscopy, X-ray crystallography, molecular dynamic simulations and site-directed in vitro mutagenesis. The receptors of several of these peptides have been identified by the use of whole-genome sequencing of spontaneous mutants of sensitive cells that have gained resistance to the peptides. Moreover, heterologous expression of these receptors in non-sensitive bacteria has been shown to render the bacteria sensitive to the peptides. The approach of whole genome sequencing of AMP/bacteriocin resistant mutants combined with heterologous expression has proved to be a widely applicable method for identification of receptors for peptide ligands.
Professors Dzung Bao Diep and Helge Holo, The Department of Chemistry, Biotechnology, and Food Science, Norwegian University of Life Sciences
Professor Yiannis Kaznessis, Department of Chemical Engineering and Materials Science, University of Minnesota
Professor Göran B. Karlsson and Anders Pedersen,Swedish NMR Centre, University of Gothenburg