Bacteriocins are a class of bacterially-produced peptides that possess an inhibitory effect on closely-related strains or species of bacteria. Glycocin F (GccF) is a di-glycosylated, 43 amino acid bacteriocin (glycocin) produced by a strain of the probiotic bacteria Lactobacillus plantarum. GccF contains two N-acetylglucosamine (GlcNAc) moieties required for its anti-bacterial activity, one O-linked through serine 18, and the other S-linked through the C-terminal cysteine located at the end of a flexible tail. Two nested disulfide bonds are also required for maintaining the folded structure. Whereas most bacteriocins exhibit bactericidal effects on a narrow range of species, GccF displays a very potent and reversible bacteriostatic activity towards a wide range of Gram positive bacteria, including vancomycin-resistant strains, making it a potentially useful scaffold for developing new compounds to combat antibiotic resistant bacteria. However, the growth-inhibiting mechanism of action of GccF remains to be elucidated.
The recent development of a complete chemical synthesis scheme for GccF enabled the production of GccF analogues, not accessible by recombinant methods, to study the role of different structural features of the peptide. Bioassays were carried out with these GccF analogues using a susceptible strain of L. plantarum. Altogether, these results provide additional evidence for a role of a GlcNAc transporter in GccF’s activity, as well as highlighting the structural aspects of this peptide that are critical for inducing stasis, including specific roles of the Ser18-O- and Cys43-S- linked sugars. The results of this work will be presented, along with a model mechanism of action.