Genetically Engineered Bacteriocins and their Potential as the Next Generation of Antimicrobials

Abstract

The discovery of penicillin by Fleming in 1928 was an historical milestone in the fight against infectious disease. Over the following fifty years, pharmaceutical companies discovered and developed over 100 antibiotics effective against a wide range of human pathogens. More recently, the dramatic rise in antibiotic-resistant pathogens has stimulated renewed efforts to identify, develop or redesign antibiotics active against these multi-resistant bacteria. This review focuses on such efforts directed at one large and highly diverse family of toxins, the bacteriocins, which hold great promise as the next generation of antimicrobials. The majority of bacteriocins differ from traditional antibiotics in one critical way: they have a relatively narrow killing spectrum and are, therefore, toxic only to bacteria closely related to the producing strain. Accordingly, they can be considered "designers drugs" that target specific bacterial pathogens. In this review we focus on recent attempts to generate custom designed bacteriocins using genetic engineering techniques. These efforts illustrate the potential of genetically-modified bacteriocins to solve some of the most challenging problems in disease control.

Cloning and Characterization of the DNA Region Responsible for Megacin A-216 Production in Bacillus megaterium 216

“…In the MALDI-TOF mass spectra of the tryptic digests of the 40-and 30-kDa protein, masses representing peptides [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and [2][3][4][5][6][7][8][9][10][11][12][13][14] of P293A were detected, which indicated that the initiating methionine residue was posttranslationally excised from a fraction of the molecules. MALDI-TOF measurements yielded an average molecular mass of 11,832 Da for the intact ␤ chain (data not shown).…”

“…The renewed interest in bacteriocins as antimicrobial agents (5,8,10) and in B. megaterium as an industrial microorganism and cloning host (38) prompted us to revisit megacinogeny of B. megaterium. The interest in B. megaterium is highlighted by the ongoing whole-genome sequencing project (http://www .bios.niu.edu/b_megaterium).…”

Prevalence of ColE1-Like Plasmids and Colicin K Production among Uropathogenic Escherichia coli Strains and Quantification of Inhibitory Activity of Colicin K

“…Due to the global concern about antibiotic resistance, novel approaches, one being the use of bacteriocins, are being considered (10,11). Colicins, bacteriocins produced by and active against Escherichia coli strains, are receiving renewed attention as an alternative means of preventing various E. coli-associated infections, for example, diarrhea, including serotype O157:H7 (15,22,28,29,30), and postweaning diarrhea and edema disease in swine (33).…”

The gene encoded antimicrobial peptides, a template for the design of novel anti-mycobacterial drugs

“…Lantibiotics have been suggested as a possible alternative to antibiotics for many drug-resistant infections. [8][9][10][11] This is due to their multiple mechanisms of action, broad-spectrum activity against a wide variety of Gram-positive targets, gene-encoded nature (making them excellent templates for bioengineering) and their ability to be delivered to the site of infection. [12][13][14] However, although lantibiotics have been extensively researched, little work has been done to investigate their application to treat mycobacterial diseases.…”