Structure-Function Relationships of the Non-Lanthionine-Containing Peptide (class II) Bacteriocins Produced by Gram-Positive Bacteria

Abstract

This review focuses on the structure and mode-of-action of non-lanthionine-containing peptide bacteriocins produced by Gram-positive bacteria. These bacteriocins may be divided into four groups: (i) the anti-listerial one-peptide pediocin-like bacteriocins that have very similar amino acid sequences, (ii) the two-peptide bacteriocins that consist of two different peptides, (iii) the cyclic bacteriocins, and (iv) the linear non-pediocin-like one-peptide bacteriocins. These bacteriocins are largely cationic, contain 20 to 70 residues, and kill cells through membrane-permeabilization. The pediocin-like bacteriocins are the ones that are best characterized. Upon contact with target membranes, their cationic N-terminal half forms a beta-sheet-like structure that binds to the target cell surface, while their more hydrophobic helical-containing C-terminal half penetrates into the hydrophobic core of target-cell membranes and apparently binds to the mannose phosphotransferase permease in a manner that results in membrane leakage. Immunity proteins that protect cells from being killed by pediocin-like bacteriocins bind to the bacteriocin-permease complex and prevent bacteriocin-induced membrane-leakage. Recent structural analyses of two-peptide bacteriocins indicate that they form a helix-helix structure that penetrates into cell membranes. Also these bacteriocins may act by binding to integrated membrane proteins. It is proposed that many membrane-active peptide bacteriocins kill target-cells through basically the same mechanism; the common theme being that a membrane-penetrating part of bacteriocins bind to a membrane embedded region of an integrated membrane protein, thereby causing conformational alterations in the protein that in turn lead to membrane-leakage and cell death.

Genetic characterisation and heterologous expression of leucocin C, a class IIa bacteriocin from Leuconostoc carnosum 4010

“…In this group, bacteriocins, such as leucocin A (LeuA) (Hastings et al 1991), mesentericin Y105 (Hechard et al 1992) and pediocin (Henderson et al 1992;Marugg et al 1992;Nieto Lozano et al 1992) have very similar amino acid sequences and contain conserved YGNGV/L "pediocin box" motif and a Cterminal disulfide bridge formed by two cysteines. According to sequence similarities in the C-terminal region, IIa bacteriocins may be further sorted into three or four subgroups Nissen-Meyer et al 2009 (Holo et al 1991;Diep et al 2007). (Cotter et al 2005a).…”

“…Class II bacteriocins have been further divided into four subgroups, of which class IIa (pediocin-like) is comprised of bacteriocins sharing an N-terminal highly conserved sequence YGNGV/L (Drider et al 2006;Nissen-Meyer et al 2009). These peptides are the best characterised, and their activity against various Lactobacillus, Enterococcus, Leuconostoc, Clostridium, and especially the pathogenic Listeria strains have caught broad attention (Eijsink et al 1998;Nissen-Meyer et al 2009).…”

“…These peptides are the best characterised, and their activity against various Lactobacillus, Enterococcus, Leuconostoc, Clostridium, and especially the pathogenic Listeria strains have caught broad attention (Eijsink et al 1998;Nissen-Meyer et al 2009). Class IIa bacteriocins permeabilise the target cells by forming pores in the cytoplasmic membrane that subsequently leads to the depletion of the intracellular ATP pool, disturbance of the proton motif force and eventually the cell death Suzuki et al 2005).…”

“…Simultaneously, the helical C-termini penetrate into the receptor protein (Johnsen et al 2005a). A hinge structure connects the two domains of a class IIa bacteriocin, facilitates the movement of either domain towards each other, and therefore mediates the pore formation (Johnsen et al 2005a;Nissen-Meyer et al 2009). …”

“…Since such receptors commonly exist on bacterial cells, these bacteriocins may also form pores on its producer cell membrane. Therefore, bacteriocin producing bacteria produce immunity proteins which bind to the bacteriocin-receptor complex from the cytosolic side of the cell membrane, and thus prevent the leakage of own membrane (Nissen-Meyer et al 2009). …”