LsbB Bacteriocin Interacts with the Third Transmembrane Domain of the YvjB Receptor

Abstract

The Zn-dependent membrane-located protease YvjB has previously been shown to serve as a target receptor for LsbB, a class II leaderless lactococcal bacteriocin. Although yvjB is highly conserved in the genus Lactococcus, the bacteriocin appears to be active only against the subspecies L. lactis subsp. lactis. Comparative analysis of the YvjB proteins of a sensitive strain (YvjB MN ) and a resistant strain (YvjB MG ) showed that they differ from each other in 31 positions. In this study, we applied site-directed mutagenesis and performed directed binding studies to provide biochemical evidence that LsbB interacts with the third transmembrane helix of YvjB in susceptible cells. The site-directed mutagenesis of LsbB and YvjB proteins showed that certain amino acids and the length of LsbB are responsible for the bacteriocin activity, most probably through adequate interaction of these two proteins; the essential amino acids in LsbB responsible for the activity are tryptophan ( Bacteriocins are small, ribosomally synthesized, cationic, and hydrophobic peptides produced by various bacteria, and they are often found to be active against bacteria closely related to the producers. However, some also have broader inhibitory spectra, including pathogens and problematic bacteria. Producer organisms are immune to their own bacteriocin(s), a property that is mediated by specific immunity proteins (1).Bacteriocins from Gram-positive bacteria are generally classified into two main groups: the class I lantibiotics, containing posttranslationally modified peptides with ring-forming lanthionine or methyllanthionine residues, and class II, composed of nonmodified or minimally modified peptide bacteriocins (1-3). Class II bacteriocins are further subdivided into pediocin-like bacteriocins (class IIa), two-peptide bacteriocins (class IIb), circular bacteriocins (class IIc), and nonpediocin one-peptide bacteriocins (class IId) (2).Bacteriocins have been much studied from a fundamental and scientific perspective and also for their potential applications as food preservatives, and in veterinary and human medicine as alternatives to antibiotics or as synergists (1, 4).Bacteriocins have a number of positive attributes that have made them especially attractive for various applications (5). Some of them exhibit a broad spectrum of activity, inhibiting microorganisms belonging to different genera and species, including many bacterial pathogens that cause human, animal, or plant infections (6). For clinical applications, bacteriocins have been presented as a viable alternative to antibiotics due to the high specificity of certain bacteriocins against clinical pathogens, including multidrug-resistant (MDR) strains (4). Therefore, these substances have various potential applications in the food industry and medicine, either alone or in combination with other chemicals or methods (7).The multiplicity and diversity of bacteriocins and the resultant effects of their interactions with targeted bacteria on microbial ecology have been thoro...

A review on Lactococcus lactis: from food to factory

“…LAB bacteriocins are antimicrobial peptides which have been ribosomally synthesized at transcriptional and post-transcriptional levels; this confers auto-immunity to the producer strain [55]. Examples of more recent bacteriocins from L. lactis include lacticin 3147 [56], lacticin Q/Z [57] and LsbB [58]. However, the most well-known and best characterised lantibiotic is nisin (term “lantibiotic” derived from Schnell [59] as lanthionine containing antibiotic), which had been discussed in depth in the preceding section.…”

The Leaderless Bacteriocin Enterocin K1 Is Highly Potent against Enterococcus faecium: A Study on Structure, Target Spectrum and Receptor

“…As mentioned elsewhere, YvjB (a homolog of RseP) serves as receptor for LsbB which binds directly to the receptor upon killing target cells (Miljkovic et al, 2016). At present it is not clear the exact role of EcsAB in the sensitivity to bacteriocins.…”

“…Recently, it has been shown that the lactococcal Zn-dependent metallopeptidase YvjB (also known as RseP) belonging to site-2 protease (S2P) protein family, serves as the receptor for LsbB (Uzelac et al, 2013; Miljkovic et al, 2016). Our previous structure-function study of LsbB provided strong evidence that the peptide binds to its receptor using its unstructured C-terminal part (Ovchinnikov et al, 2014).…”

Circular and Leaderless Bacteriocins: Biosynthesis, Mode of Action, Applications, and Prospects

“…The outmost 8-amino acid sequence at the C-terminal end of LsbB has been shown to contain the receptor binding domain ( Ovchinnikov et al, 2014 ). Further analyses have shown that the receptor-binding domain of LsbB interacts with the highly conserved Tyr 356 and Ala 353 residues at the third transmembrane domain of YvjB ( Miljkovic et al, 2016 ). They further hypothesized that this killing mechanism is common among LsbB-related leaderless bacteriocins such as enterocins Q, K1, and EJ97 ( Ovchinnikov et al, 2014 , 2017 ).…”