New insights into the mode of action of the lantibiotic salivaricin B

Abstract

Salivaricin B is a 25 amino acid polycyclic peptide belonging to the type AII lantibiotics and first shown to be produced by Streptococcus salivarius. In this study we describe the bactericidal mode of action of salivaricin B against susceptible Gram-positive bacteria. The killing action of salivaricin B required micro-molar concentrations of lantibiotic whereas the prototype lantibiotic nisin A was shown to be potent at nano-molar levels. Unlike nisin A, salivaricin B did not induce pore formation or dissipate the membrane potential in susceptible cells. This was established by measuring the fluorescence of the tryptophan residue at position 17 when salivaricin B interacted with bacterial membrane vesicles. The absence of a fluorescence blue shift indicates a failure of salivaricin B to penetrate the membranes. On the other hand, salivaricin B interfered with cell wall biosynthesis, as shown by the accumulation of the final soluble cell wall precursor UDP-MurNAc-pentapeptide which is the backbone of the bacterial peptidoglycan. Transmission electron microscopy of salivaricin B-treated cells showed a reduction in cell wall thickness together with signs of aberrant septum formation in the absence of visible changes to cytoplasmic membrane integrity.

Probing key elements of teixobactin–lipid II interactions in membranes

“…The minimal inhibitory concentrations of nisin, when calculated in molar concentrations, fall within a sub-micromolar range 42,43. This range corresponds to the same order of magnitude as wildtype Txb.…”

Analysis of the Inhibitory Potential of Clinical Streptococcus Salivarius Isolates From Saliva and Dorsal of Tongue of Adults on Enterococcal Faecalis Growth

“…Another mechanism that is different is expressed also by previous study indicating that the mechanism of Type B lantibiotic as seen in SalB. SalB works by inducing the accumulation of a precursor (UDP-MurNAcpentapeptide) from the end of the cell wall, thus causing obstacles to biosynthesis within the cell walls [26]. The observed differences are also due to its antimicrobial activity.…”

“…The diversity of the types of lantibiotic proteins depend on the type of S. salivarius. The differences in the results of inhibition zone produced by saliva and dorsal tongue swab isolates may be due to differences in the types of protein produced by the different isolates [26].…”

Analysis of the Potential of Streptococcus Salivarius Isolated From the Saliva and Tongue Dorsum to Inhibit the Growth of Fusobacterium Nucleatum

“…In general, lantibiotic interferes with the integrity of the cytoplasmic membrane by forming pores and inhibiting the biosynthesis of cell walls [17,19]. As explained previously, lantibiotic can work on Gram-negative bacteria only if the bacteria's outer membrane is compromised [20], which can be accomplished only by lantibiotic that is relatively large (1800-4600 Da) [21].…”

“…MacDonald's study used S. salivarius K12 and M18, reas the present study used S. salivarius 13,491 (control) and a clinical strain [16]. One of the lantibiotics secreted by S. salivarius K12 and M18 is salivaricin B, which instead of forming pores on the cell's membranes, resists the transglycosylation that leads to inhibition of the cell wall's biosynthesis [17]. That was why in the study, salivaricin appeared only to reduce the thickness of the cell walls.…”