Thusin, a Novel Two-Component Lantibiotic with Potent Antimicrobial Activity against Several Gram-Positive Pathogens

Abstract

Due to the rapidly increasing prevalence of multidrug-resistant bacterial strains, the need for new antimicrobial drugs to treat infections has become urgent. Bacteriocins, which are antimicrobial peptides of bacterial origin, are considered potential alternatives to conventional antibiotics and have attracted widespread attention in recent years. Among these bacteriocins, lantibiotics, especially two-component lantibiotics, exhibit potent antimicrobial activity against some clinically relevant Gram-positive pathogens and have potential applications in the pharmaceutical industry. In this study, we characterized a novel two-component lantibiotic termed thusin that consists of Thsα, Thsβ, and Thsβ' (mutation of Thsβ, A14G) and that was isolated from a B. thuringiensis strain BGSC 4BT1. Thsα and Thsβ (or Thsβ') exhibit optimal antimicrobial activity at a 1:1 ratio and act sequentially to affect target cells, and they are all highly thermostable (100°C for 30 min) and pH tolerant (pH 2.0 to 9.0). Thusin shows remarkable efficacy against all tested Gram-positive bacteria and greater activities than two known lantibiotics thuricin 4A-4 and ticin A4, and one antibiotic vancomycin against various bacterial pathogens (Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus (MRSA), Staphylococcus sciuri, Enterococcus faecalis, and Streptococcus pneumoniae). Moreover, thusin is also able to inhibit the outgrowth of B. cereus spores. The potent antimicrobial activity of thusin against some Gram-positive pathogens indicates that it has potential for the development of new drugs.

Roseocin, a novel two‐component lantibiotic from an actinomycete

“…As with the other two‐component lantibiotics (Begley et al, ; Xin et al, ), roseocin peptides displayed synergistic antimicrobial activity primarily against the Gram‐positive bacteria and only weak activity, if any, against the Gram‐negative bacteria. Initially, the peptides were treated with GluC to remove most of the leader, leaving a trace of 4 and 12 residues in RosA2α′ and RosA1β′, respectively (Figure c,d).…”

“…Hence, it could not be studied further due to the absence of the second gene product. Though attempts were not made to characterize roseocin from S. roseosporus NRRL 11379, however, heterologous production of the two modified RosA peptides and in vitro leader peptide removal for generation of bioactive lanthipeptides, led to the bioactivity evaluation and partial structural analysis of the encoded two-component lantibiotic, roseocin.As with the other two-component lantibiotics(Begley et al, 2009;Xin et al, 2016), roseocin peptides displayed synergistic antimicrobial activity primarily against the Gram-positive bacteria and only weak activity, if any, against the Gram-negative bacteria.…”

Mechanisms and consequences of intestinal dysbiosis

“…Beyond their contribution in the development of dysbiosis during inflammation, bacteriocins represent interesting candidate drugs aiming at the selective inhibition of pathogenic bacteria resistant to conventional antibiotics, such as C. difficile [187] and methicillin-resistant Staphylococcus aureus [188].…”

Biomanufacturing process for the production of bacteriocins from Bacillaceae family

“…Entomocin 110 had a relatively wide spectrum of microbial inhibition against many Bacillus species while purified Bac IH7 displayed a wide inhibitory bacteriocidal activity towards G+ve/G−ve bacteria and fungal pathogens (Cherif et al 2008;He et al 2007;Hammami et al 2011). Thusin, a two-component lantibiotic consists of Thsα, Thsβ/Thsβʹ, exhibited remarkably efficient antimicrobial activity against B. cereus (cells and spores), L. monocytogenes, S. sciuri, E. faecalis and S. pneumoniae (Xin et al 2016). The previously mentioned bacteriocin showed superior activities against methicillin-resistant Staphylococcus aureus, as compared to that of discovered lantibiotics (e.g.…”