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

Panina, Irina; Balandin, Sergey V.; Tsarev, Andrey V.; Chugunov, Anton O.; Tagaev, Andrey A.; Finkina, Ekaterina I.; Antoshina, Daria V.; Sheremeteva, Elvira V.; Paramonov, Alexander S.; Rickmeyer, Jasmin; Bierbaum, Gabriele; Efremov, Roman G.; Шенкарев, Захар О.; Ovchinnikova, Tatiana V.

doi:10.3390/ijms24021332

Cited by 11 publications

(4 citation statements)

References 68 publications

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“…The lantibiotic is a peptide antibiotic (lanthionine) that is active on Gram-positive bacteria. Depolarization of the bacterial-energized cytoplasmic membrane is the basis for its bactericidal activity, and this is initiated by the formation of aqueous transmembrane pores (Panina et al 2023 ). Our results show that ethyl acetate extract of fermentation products of Bacillus sp.…”

Section: Discussionmentioning

confidence: 99%

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Eltokhy,

Saad,

Eltayeb

et al. 2024

AMB Expr

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Multidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052.

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Section: Discussionmentioning

confidence: 99%

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Eltokhy,

Saad,

Eltayeb

et al. 2024

AMB Expr

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“…Lichenicidin acts through a dual mode of action that involves the α subunit recognition of lipid II, providing specificity and stability for the interaction of β subunit, which induces leakage of the intracellular contents of bacteria [ 94 , 95 ] ( Figure 2 ).…”

Section: Antibacterial Substances Secreted By Bacillus Lich...mentioning

confidence: 99%

Bacillus licheniformis: A Producer of Antimicrobial Substances, including Antimycobacterials, Which Are Feasible for Medical Applications

Shleeva,

Kondratieva,

Kaprelyants

2023

Pharmaceutics

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Bacillus licheniformis produces several classes of antimicrobial substances, including bacteriocins, which are peptides or proteins with different structural composition and molecular mass: ribosomally synthesized by bacteria (1.4–20 kDa), non-ribosomally synthesized peptides and cyclic lipopeptides (0.8–42 kDa) and exopolysaccharides (>1000 kDa). Different bacteriocins act against Gram-positive or Gram-negative bacteria, fungal pathogens and amoeba cells. The main mechanisms of bacteriocin lytic activity include interaction of peptides with membranes of target cells resulting in structural alterations, pore-forming, and inhibition of cell wall biosynthesis. DNase and RNase activity for some bacteriocines are also postulated. Non-ribosomal peptides are synthesized by special non-ribosomal multimodular peptide synthetases and contain unnatural amino acids or fatty acids. Their harmful effect is due to their ability to form pores in biological membranes, destabilize lipid packaging, and disrupt the peptidoglycan layer. Lipopeptides, as biosurfactants, are able to destroy bacterial biofilms. Secreted polysaccharides are high molecular weight compounds, composed of repeated units of sugar moieties attached to a carrier lipid. Their antagonistic action was revealed in relation to bacteria, viruses, and fungi. Exopolysaccharides also inhibit the formation of biofilms by pathogenic bacteria and prevent their colonization on various surfaces. However, mechanism of the harmful effect for many secreted antibacterial substances remains unknown. The antimicrobial activity for most substances has been studied in vitro only, but some substances have been characterized in vivo and they have found practical applications in medicine and veterinary. The cyclic lipopeptides that have surfactant properties are used in some industries. In this review, special attention is paid to the antimycobacterials produced by B. licheniformis as a possible approach to combat multidrug-resistant and latent tuberculosis. In particular, licheniformins and bacitracins have shown strong antimycobacterial activity. However, the medical application of some antibacterials with promising in vitro antimycobacterial activity has been limited by their toxicity to animals and humans. As such, similar to the enhancement in the antimycobacterial activity of natural bacteriocins achieved using genetic engineering, the reduction in toxicity using the same approach appears feasible. The unique capability of B. licheniformis to synthesize and produce a range of different antibacterial compounds means that this organism can act as a natural universal vehicle for antibiotic substances in the form of probiotic cultures and strains to combat various types of pathogens, including mycobacteria.

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“…Most bacteriocins are cationic and interact with negatively charged bacterial membranes due to electrostatic forces, similarly to cationic antimicrobial peptides in multicellular organisms [78]. Electrostatic interactions occur between the negatively charged teichoic acids and phospholipids of Gram-positive bacteria, as well as with lipopolysaccharides of Gram-negative bacteria, and with Lipid II, which is a precursor molecule in the synthesis of the cell wall of both Gram-positive and Gram-negative bacteria [79]. This interaction represents the first stage in the manifestation of nonspecific and specific activity [34].…”

Section: Mechanism Of Action On Microorganismsmentioning

confidence: 99%

Immunomodulation, Bioavailability and Safety of Bacteriocins

Guryanova

2023

Life

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The rise of antibiotic-resistant bacteria and the emergence of new pathogens have created a need for new strategies to fight against infectious diseases. One promising approach is the use of antimicrobial peptides produced by a certain species of bacteria, known as bacteriocins, which are active against other strains of the same or related species. Bacteriocins can help in the treatment and prevention of infectious diseases. Moreover, bacteriocins can be obtained in prokaryotic organisms, and contribute s to their widespread use. While the use of bacteriocins is currently limited to the food industry (for example, nisin is used as a preservative, E234), a large number of studies on their microbicidal properties suggest that their use in medicine may increase in the foreseeable future. However, for the successful use of bacteriocins in medicine, it is necessary to understand their effect on the immune system, especially in cases where immunity is weakened due to infectious processes, oncological, allergic, or autoimmune diseases. Studies on the immuno-modulatory activity of bacteriocins in animal models and human cells have revealed their ability to induce both pro-inflammatory and anti-inflammatory factors involved in the implementation of innate immunity. The influence of bacteriocins on acquired immunity is revealed by an increase in the number of T-lymphocytes with a simultaneous decrease in B-lymphocyte levels, which makes them attractive substances for reducing inflammation. The widespread use of bacteriocins in the food industry, their low toxicity, and their broad and narrow specificity are reasons for researchers to pay attention to their immunomodulatory properties and explore their medical applications. Inflammation regulation by bacteriocins can be used in the treatment of various pathologies. The aim of the review was to analyze scientific publications on the immunomodulatory activity, bioavailability, and safety of bacteriocins in order to use the data obtained to organize preclinical and clinical studies.

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

Cited by 11 publications

References 68 publications

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Bacillus licheniformis: A Producer of Antimicrobial Substances, including Antimycobacterials, Which Are Feasible for Medical Applications

Immunomodulation, Bioavailability and Safety of Bacteriocins

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