Team:SDU-Denmark/Bacteriocin
Bacteriocins
Overview
Bacteriocins are antimicrobial peptide compounds that are ribosomally produced by gram-positive or gram-negative bacteria as inactive or active pre-peptides ZENDO, T. (2013). Screening and Characterization of Novel Bacteriocins from Lactic Acid Bacteria. Bioscience, Biotechnology, and Biochemistry, 77(5), 893–899. Bacteriocins are first discussed in 1925 by Gratia, they are reported as highly specific antibiotics produced by E. coli Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142..The bacteriocins show bacteriostatic or/and bactericidal activity against other related bacteria, and can be broad- or narrow-spectrum Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142.. The bacteriocins effect through adhesion to specific receptors present of the external surface of the target bacteria, or by other unknown mechanism Zendo, T., Yoneyama, F., & Sonomoto, K. (2010). Lactococcal membrane-permeabilizing antimicrobial peptides. Hereby the bacteriocins induce metabolic changes by forming an open pore where nutrients diffuse out of the cell and therefore also morphological changes, which might result in the death of the bacteria or inhibition of its virulence factors. The bacteriocins are found to play a fundamental role in controlling pathogenic and non-wanted flora as well as establish beneficial bacterial populations and they thus serve as an alternative and/or supplement of traditional antibiotics used today, thereby facing the problem of antimicrobial resistance (AMR).
Gene localization and regulation
The bacteriocins are located in operons clusters. These clusters contain genes encoding the bacteriocin, corresponding immunity and furthermore genes that encodes peptides responsible for post translational modification Zacharof, M. P., & Lovitt, R. W. (2012). Bacteriocins Produced by Lactic Acid Bacteria A Review Article. APCBEE Procedia, 2(2), 50–56. . The operon can be located either on plasmids, chromosomes or transposons of either plasmids or chromosomes, which serve to the complexity of the bacteriocins. However most bacteriocin operons are located on plasmids as it has been suggested to help the phylogenetic dissemination of bacteriocins among lactic acid bacteria (LAB) Zacharof, M. P., & Lovitt, R. W. (2012). Bacteriocins Produced by Lactic Acid Bacteria A Review Article. APCBEE Procedia, 2(2), 50–56.
The immunity systems makes the bacteriocin-producing bacteria resistant towards its own bacteriocin Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142.. For the bacteriocins produced by Gram positive LAB there are two types of immunity systems known today. The first being the Lan I protein which provides immunity to the producer cell by being attached to the outside of the cytoplasmic membrane of the producing cell. The localization prevents pore formation by the bacteriocin molecule as the Lan I protein continuously transport the bacteriocin molecule, that have been inserted into the membrane, back to the surrounding medium. The second immunity system depends on separate dedicated multicomponent ABC transporter called LAN EFG Zacharof, M. P., & Lovitt, R. W. (2012). Bacteriocins Produced by Lactic Acid Bacteria A Review Article. APCBEE Procedia, 2(2), 50–56. . However the mechanism of immunity systems are similar in their way of functioning, as they in general work by removing the bacteriocin or by competitive inhibition of the bacteriocin receptor Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142..
The regulation of the bacteriocin expression is a subject for external induction factors (IF). The regulating system is composed of three components; an inducing peptide - either IF or pheromone-activating factors, a trans-membrane histidine kinase or a pheromone receptor and a response regulator Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142.. IF are small peptides that are ribosomally synthesized at low levels as a pre-peptide and are cleaved before secretion. IF factors are either secreted by the bacteriocin producer-strain itself or concurrent of the bacteriocin producing strain Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142.. The possibility of the production of IF factors by other strains makes the regulatory and controllable aspect of bacteriocin production of a specific strain a target for quorum sensing. IF binds to the correspondent histidine protein kinase and thus activate it to phosphorylate a response regulator, which then stimulates the transcription of target genes by, binding to specific repeats that are present in many bacteriocin operons. The bacteriocin production is thereby autoregulated by the inducer peptide (IF) making it possible for the respective strain to possess positive or negative feedback or to be regulated, or even to regulate, related or competing strains. The production of IF are dependent of environmental conditions such as temperature, pH.
Bacteriocin secretion
The proteinaceous bacteriocins are secreted out of the bacteria cell in their exponential growth phase by guidance of their respective N-terminal leader sequence Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142.. Through the export process the leader sequence are proteolytically processed and some of the peptides are posttranslational modified. The export thus results in the fully mature and active peptide through enzymatically modification Zacharof, M. P., & Lovitt, R. W. (2012). Bacteriocins Produced by Lactic Acid Bacteria A Review Article. APCBEE Procedia, 2(2), 50–56. , Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142.. Bacteriocins produced by gram-positive lactic acid bacteria (LAB) are defined as GRAS (Generally recognized as safe) and/or probiotics as their presence serve to provide an advantage in the human gastrointestinal tract Balciunas, E. M., Castillo Martinez, F. A., Todorov, S. D., Gombossy De Melo Franco, B. D., Converti, A., & Pinheiro De Souza Oliveira, R. (2013). Novel biotechnological applications of bacteriocins: A review. Food Control, 32, 134–142..
