Mode of action of modified and unmodified bacteriocins from Gram-positive bacteria

Abstract

The antibiotic activity of bacteriocins from Gram-positive bacteria, whether they are modified (class I bacteriocins, lantibiotics) or unmodified (class II), is based on interaction with the bacterial membrane. However, recent work has demonstrated that for many bacteriocins, generalised membrane disruption models as elaborated for amphiphilic peptides (e.g. tyriodal pore or carpet model) cannot adequately describe the bactericidal action. Rather, specific targets seem to be involved in pore formation and other activities. For the nisin and epidermin family of lantibiotics, the membrane-bound cell wall precursor lipid II has recently been identified as target. The duramycin family of lantibiotics binds specifically to phosphoethanolamine which results in inhibition of phospholipase A2 and various other cellular functions. Most of the class II bacteriocins dissipate the proton motive force (PMF) of the target cell, via pore formation. The subclass IIa bacteriocin activity likely depends on a mannose permease of the phosphotransferase system (PTS) as specific target. The subclass IIb bacteriocins (two-component) also induce dissipation of the PMF by forming cation- or anion-specific pores; specific targets have not yet been identified. Finally, the subclass IIc comprises miscellaneous peptides with various modes of action such as membrane permeabilization, specific inhibition of septum formation and pheromone activity.