Insights into the mode of action of the two-peptide lantibiotic lichenicidin

Barbosa, Joana; Gonçalves, Sónia; Makowski, Marcin; Silva, Ítala C.; Caetano, Tânia; Schneider, Tanja; Mösker, Eva; Santos, Nuno C.; Mendo, Sónia

doi:10.1016/j.colsurfb.2021.112308

Cited by 11 publications

(7 citation statements)

References 46 publications

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“…A prediction for the biosynthesis and final structures of two peptides was carried out based on the known modifications to the sequence-related lantibiotics lacticin 3147 and lichenicidin. Lichenicidin A1 and A2 core peptides share 40% and 44.7% sequence identity with the LanA1 and LanA2, respectively ( 23 ) (see Fig. 4 ).…”

Section: Resultsmentioning

confidence: 99%

The novel bacteriocin romsacin from Staphylococcus haemolyticus inhibits Gram-positive WHO priority pathogens

Wolden,

Ovchinnikov,

Venter

et al. 2023

Microbiol Spectr

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Staphylococcus haemolyticus is an increasingly relevant nosocomial pathogen. The combination of multi-drug resistance and ability to form biofilms makes S. haemolyticus infections difficult to treat. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria to inhibit growth of often closely related bacteria. Due to differences in the modes of action between bacteriocins and antibiotics, bacteriocins are normally equally potent against antibiotic-resistant and antibiotic-sensitive strains. To find bacteriocins able to inhibit S. haemolyticus and related species, clinical and commensal S. haemolyticus isolates ( n = 174) were assayed for bacteriocin production. One commensal isolate produced an antimicrobial substance inhibiting S. haemolyticus and Staphylococcus aureus . The substance had physicochemical properties that are characteristic of bacteriocins. Purification, whole-genome sequencing, and mass spectrometry identified the antimicrobial as a novel two-peptide lantibiotic, hereafter named romsacin. The bacteriocin was active against a broad range of Gram-positive bacteria, such as the World Health Organization priority pathogens S. aureus [methicillin-resistant S. aureus (MRSA)] and Enterococcus faecium [vancomycin-resistant E. faecium (VRE)]. Importantly, the bacteriocin also eradicated S. haemolyticus , Staphylococcus epidermidis , MRSA, and VRE biofilms. IMPORTANCE Bacteria produce bacteriocins to inhibit growth of other bacterial species. We have studied the antimicrobial activity of a new bacteriocin produced by the skin bacterium S. haemolyticus . The bacteriocin is effective against several types of Gram-positive bacteria, including highly virulent and antibiotic-resistant strains such as Staphylococcus aureus and Enterococcus faecium . Effective antimicrobials are important for the treatment of infections and the success of major surgery and chemotherapy. Bacteriocins can be part of the solution to the global concern of antimicrobial resistance.

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Section: Resultsmentioning

confidence: 99%

The novel bacteriocin romsacin from Staphylococcus haemolyticus inhibits Gram-positive WHO priority pathogens

Wolden,

Ovchinnikov,

Venter

et al. 2023

Microbiol Spectr

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“…Despite the identity of the amino acid sequences of the precursor and the same dehydration sites, the N -terminal domain of Licα contains the Dha5–Cys7 lanthionine bridge and two Dhb residues (in positions 3 and 6). Surprisingly, the β-components of the two lantibiotics (Lchβ and Licβ) are identical and exhibit synergistic effects with both α-peptide variants [ 19 , 37 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent carboxyfluorescein leakage experiments with liposomes of different composition and lichenicidin I89 (a natural variant of lichenicidin isolated from the Bacillus licheniformis I89 strain and composed of Licα and Licβ) have pointed to the role of lipid II as a landing site for Licα, as was previously proposed for other lantibiotics [ 37 ]. The aim of this work was to elucidate the mechanism of lipid II binding by Lchα and to reveal roles of both putative binding sites using in vitro and in silico approaches.…”

Section: Introductionmentioning

confidence: 99%

Specific Binding of the α-Component of the Lantibiotic Lichenicidin to the Peptidoglycan Precursor Lipid II Predetermines Its Antimicrobial Activity

Panina

Balandin

Tsarev

et al. 2023

IJMS

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To date, a number of lantibiotics have been shown to use lipid II—a highly conserved peptidoglycan precursor in the cytoplasmic membrane of bacteria—as their molecular target. The α-component (Lchα) of the two-component lantibiotic lichenicidin, previously isolated from the Bacillus licheniformis VK21 strain, seems to contain two putative lipid II binding sites in its N-terminal and C-terminal domains. Using NMR spectroscopy in DPC micelles, we obtained convincing evidence that the C-terminal mersacidin-like site is involved in the interaction with lipid II. These data were confirmed by the MD simulations. The contact area of lipid II includes pyrophosphate and disaccharide residues along with the first isoprene units of bactoprenol. MD also showed the potential for the formation of a stable N-terminal nisin-like complex; however, the conditions necessary for its implementation in vitro remain unknown. Overall, our results clarify the picture of two component lantibiotics mechanism of antimicrobial action.

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“…This assay, developed by Lehrer et al in the late 1980 s, [88] has been widely applied for studying inner membrane permeabilization. [89,90] These kinds of studies allow comparison and evaluation of the extent of damage from the outer and inner membranes in gram-negative bacteria. Usually, while outer membrane damage occurs rapidly and at lower AMP concentrations, the inner membrane requires longer times and higher peptide concentrations.…”

Section: In Vivo Assessment Of Amp-induced Permeabilitymentioning

confidence: 99%

Membrane permeability and antimicrobial peptides: Much more than just making a hole

et al. 2023

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Antimicrobial peptides (AMPs) are one of the elements of innate immunity that have a crucial role in fighting infections. These molecules are produced by all kinds of cells and can display a wide spectrum of action against bacterial or fungal infections. Bacterial resistance toward broad‐spectrum antibiotics has become a major concern in recent years. In this context, AMPs have emerged as promising alternative therapy in response to this increasing problem because of their ability to inhibit growth and biofilm formation, even in drug‐resistant microorganisms. However, despite the myriad of patents filed related to AMPs, only a small proportion of AMPs have already received certification, either by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In order to pave the way of AMPs to certification, a comprehensive knowledge of the mechanism of action of these peptides is essential. Several models have been proposed to explain it and the permeabilization of the bacterial envelope seems to play a key role in most of them. In this review, we describe the different techniques that are generally used to assess the permeabilization induced by AMPs in either in vivo or in vitro systems. Additionally, a comprehensive analysis of the cooperation during the process of binding and permeabilization is included.

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Insights into the mode of action of the two-peptide lantibiotic lichenicidin

Cited by 11 publications

References 46 publications

The novel bacteriocin romsacin from Staphylococcus haemolyticus inhibits Gram-positive WHO priority pathogens

The novel bacteriocin romsacin from Staphylococcus haemolyticus inhibits Gram-positive WHO priority pathogens

Specific Binding of the α-Component of the Lantibiotic Lichenicidin to the Peptidoglycan Precursor Lipid II Predetermines Its Antimicrobial Activity

Membrane permeability and antimicrobial peptides: Much more than just making a hole

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