Heterologous Expression and Characterization of Estercin A, a Class II Lanthipeptide Derived from CF016, with Antimicrobial Activity against Clinically Relevant Pathogens.

Recent genome mining work revealed that unexplored habitats exhibit great potential for discovering new nonribosomal peptides (NRPs) and ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides are a group of RiPPs exhibiting a variety of biological functions. They are characterized by the presence of the thioether-containing bis-amino acids lanthionine and/or methyllanthionine.

Biosynthesis of Antimicrobial Ornithine-Containing Lacticin 481 Analogues by Use of a Combinatorial Biosynthetic Pathway in .

Lacticin 481, a ribosomally synthesized and post-translationally modified peptide (RiPP), exhibits antimicrobial activity, for which its characteristic lanthionine and methyllanthionine ring structures are essential. The post-translational introduction of (methyl)lanthionines in lacticin 481 is catalyzed by the enzyme LctM. In addition to macrocycle formation, various other post-translational modifications can enhance and modulate the chemical and functional diversity of antimicrobial peptides.

Synechococsins: Lanthipeptides acting as defensive signals to disarm offensive competitors?

Synechococsins represent a diverse group of class II lanthipeptides from the prochlorosin family, produced by the marine picocyanobacterium Synechococcus. A single strain can produce multiple SyncA peptides through modification by SyncM, a bifunctional lanthipeptide synthetase. Despite the prevalence of these lanthipeptides in nature, their biological functions remain elusive, even for the most studied group, Prochlorococcus MIT9313.

Discovery, Biosynthesis, and Characterization of Rodencin, a Two-Component Lanthipeptide, Harboring d-Amino Acids Introduced by the Unusual Dehydrogenase RodJ.

Lanthipeptides, a group of ribosomally synthesized and post-translationally modified peptides (RiPPs), exhibit diverse structures and bioactivities. Their biosynthetic enzymes serve as valuable tools for peptide bioengineering. Here, we report a class II lanthipeptide biosynthetic gene cluster in a strain, driving the biosynthesis of a two-component lanthipeptide, termed rodencin, featured by the presence of two different d-amino acids, i.

Bismuth-based drugs sensitize Pseudomonas aeruginosa to multiple antibiotics by disrupting iron homeostasis.

Pseudomonas aeruginosa infections are difficult to treat due to rapid development of antibiotic drug resistance. The synergistic combination of already-in-use drugs is an alternative to developing new antibiotics to combat antibiotic-resistant bacteria. Here we demonstrate that bismuth-based drugs (bismuth subsalicylate, colloidal bismuth subcitrate) in combination with different classes of antibiotics (tetracyclines, macrolides, quinolones, rifamycins and so on) can eliminate multidrug-resistant P.

An Engineered Nisin Analogue with a Hydrophobic Moiety Attached at Position 17 Selectively Inhibits Strains.

Antibiotic resistance is one of the most challenging global public health concerns. It results from the misuse and overuse of broad-spectrum antibiotics, which enhance the dissemination of resistance across diverse bacterial species. Antibiotics like nisin and teixobactin do not target an essential protein and employ a dual mode of action antibacterial mechanism, thereby being less prone to induce resistance.

Community context influences the conjugation efficiency of .

In urinary tract infections (UTIs), different bacteria can live in a polymicrobial community consisting of different species. It is unknown how community members affect the conjugation efficiency of uropathogenic . We investigated the influence of individual species often coisolated from urinary infections (UTI) on the conjugation efficiency of isolates in artificial urine medium.

Facile Halogenation of Antimicrobial Peptides As Demonstrated by Producing Bromotryptophan-Labeled Nisin Variants with Enhanced Antimicrobial Activity.

Antimicrobial peptides (AMPs) have raised significant interest, forming a potential new class of antibiotics in the fight against multi-drug-resistant bacteria. Various AMPs are ribosomally synthesized and post-translationally modified peptides (RiPPs). One post-translational modification found in AMPs is the halogenation of Trp residues.

A systematic comparison of natural product potential, with an emphasis on RiPPs, by mining of bacteria of three large ecosystems.

The implementation of several global microbiome studies has yielded extensive insights into the biosynthetic potential of natural microbial communities. However, studies on the distribution of several classes of ribosomally synthesized and post-translationally modified peptides (RiPPs), non-ribosomal peptides (NRPs) and polyketides (PKs) in different large microbial ecosystems have been very limited. Here, we collected a large set of metagenome-assembled bacterial genomes from marine, freshwater and terrestrial ecosystems to investigate the biosynthetic potential of these bacteria.

Temperature dependence of the mutation rate towards antibiotic resistance.

Objectives: Environmental conditions can influence mutation rates in bacteria. Fever is a common response to infection that alters the growth conditions of infecting bacteria. Here we examine how a temperature change, such as is associated with fever, affects the mutation rate towards antibiotic resistance.

A two-step regulatory circuit involving Spo0A-AbrB activates mersacidin biosynthesis in Bacillus subtilis.

Due to intramolecular ring structures, the ribosomally produced and post-translationally modified peptide mersacidin shows antimicrobial properties comparable to those of vancomycin without exhibiting cross-resistance. Although the principles of mersacidin biosynthesis are known, there is no information on the molecular control processes for the initial stimulation of mersacidin bioproduction. By using Bacillus subtilis for heterologous biosynthesis, a considerable amount of mersacidin could be produced without the mersacidin-specific immune system and the mersacidin-activating secretory protease.

Identification of metabolites produced by six gut commensal Bacteroidales strains using non-targeted LC-MS/MS metabolite profiling.

As the most abundant gram-negative bacterial order in the gastrointestinal tract, Bacteroidales bacteria have been extensively studied for their contribution to various aspects of gut health. These bacteria are renowned for their involvement in immunomodulation and their remarkable capacity to break down complex carbohydrates and fibers. However, the human gut microbiota is known to produce many metabolites that ultimately mediate important microbe-host and microbe-microbe interactions.

Engineering circular bacteriocins: structural and functional effects of α-helix exchanges and disulfide introductions in circularin A.

Circular bacteriocins form a distinct group of antimicrobial peptides (AMPs) characterized by their unique head-to-tail ligated circular structure and functional properties. They belong to the ribosomally synthesized and post-translationally modified peptide (RiPP) family. The ribosomal origin of these peptides facilitates rapid diversification through mutations in the precursor genes combined with specific modification enzymes.

Engineering hybrid lantibiotics yields the highly stable and bacteriocidal peptide cerocin V.

Antimicrobial peptides (AMPs) show promise as alternatives to traditional antibiotics for treating drug-resistant infections. Their adaptability and diverse sequence possibilities allow for rational design by modulating physicochemical determinants to achieve desired biological properties, transforming them into peptides for potential new therapies. Nisin, one of the best-studied AMPs, is believed to have potential to be used as a therapeutic, particularly against antibiotic-resistant bacteria.

Selective Aza-Michael Addition to Dehydrated Amino Acids in Natural Antimicrobial Peptides.

We report the efficient and site selective modification of non-canonical dehydroamino acids in ribosomally synthesized and post-transationally modified peptides (RiPPs) by β-amination. The singly modified thiopeptide Thiostrepton showed an up to 35-fold increase in water solubility, and minimum inhibitory concentration (MIC) assays showed that antimicrobial activity remained good, albeit lower than the unmodified peptide. Also the lanthipeptide nisin could be modified using this method.

In Vitro Influence of Specific Bacteroidales Strains on Gut and Liver Health Related to Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major health risk and a serious worldwide issue. MAFLD typically arises from aberrant lipid metabolism, insulin resistance, oxidative stress, and inflammation. However, subjacent causes are multifactorial.

Altering Specificity and Enhancing Stability of the Antimicrobial Peptides Nisin and Rombocin through Dehydrated Amino Acid Residue Engineering.

Nisin serves as the prototype within the lantibiotic group of antimicrobial peptides, exhibiting a broad-spectrum inhibition against Gram-positive bacteria, including important food-borne pathogens and clinically relevant antibiotic-resistant strains. The gene-encoded nature of nisin allows for gene-based bioengineering, enabling the generation of novel derivatives. It has been demonstrated that nisin mutants can be produced with improved functional properties.

Rombocin, a Short Stable Natural Nisin Variant, Displays Selective Antimicrobial Activity against and Employs a Dual Mode of Action to Kill Target Bacterial Strains.

Nisin, with its unique mode of action and potent antimicrobial activity, serves as a remarkable inspiration for the design of novel antibiotics. However, peptides possess inherent weaknesses, particularly their susceptibility to proteolytic degradation, such as by trypsin, which limits their broader applications. This led us to speculate that natural variants of nisin produced by underexplored bacterial species can potentially overcome these limitations.

Uncovering the diversity and distribution of biosynthetic gene clusters of prochlorosins and other putative RiPPs in marine strains.

Genome mining studies have revealed the remarkable combinatorial diversity of ribosomally synthesized and post-translationally modified peptides (RiPPs) in marine bacteria, including prochlorosins. However, mining strategies also prove valuable in investigating the genomic landscape of associated genes within biosynthetic gene cluster (BGC) specific to targeted RiPPs of interest. Our study contributes to the enrichment of knowledge regarding prochlorosin diversity.

Food safety and biological control; genomic insights and antimicrobial potential of Bacillus velezensis FB2 against agricultural fungal pathogens.

Development of natural, broad-spectrum, and eco-friendly bio-fungicides is of high interest in the agriculture and food industries. In this context, Bacillus genus has shown great potential for producing a wide range of antimicrobial metabolites against various pathogens. A Bacillus velezensis strain FB2 was isolated from an agricultural field of National Institute for Biotechnology and Genetic Engineering (NIBGE) Faisalabad, Pakistan, exhibiting good antifungal properties.

Systematic analysis of drug combinations against Gram-positive bacteria.

Drug combinations can expand options for antibacterial therapies but have not been systematically tested in Gram-positive species. We profiled ~8,000 combinations of 65 antibacterial drugs against the model species Bacillus subtilis and two prominent pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Thereby, we recapitulated previously known drug interactions, but also identified ten times more novel interactions in the pathogen S.

Cesin, a short natural variant of nisin, displays potent antimicrobial activity against major pathogens despite lacking two C-terminal macrocycles.

Nisin is a widely used lantibiotic owing to its potent antimicrobial activity and its food-grade status. Its mode of action includes cell wall synthesis inhibition and pore formation, which are attributed to the lipid II binding and pore-forming domains, respectively. We discovered cesin, a short natural variant of nisin, produced by the psychrophilic anaerobe .

Seeing the Invisibles: Detection of Peptide Enantiomers, Diastereomers, and Isobaric Ring Formation in Lanthipeptides Using Nanopores.

Mass spectrometry (MS) is widely used in proteomic analysis but cannot differentiate between molecules with the same mass-to-charge ratio. Nanopore technology might provide an alternative method for the rapid and cost-effective analysis and sequencing of proteins. In this study, we demonstrate that nanopore currents can distinguish between diastereomeric and enantiomeric differences in l- and d-peptides, not observed by conventional MS analysis, down to individual d-amino acids in small opioid peptides.

Bioinformatic mining for RiPP biosynthetic gene clusters in Bacteroidales reveals possible new subfamily architectures and novel natural products.

The Bacteroidales order, widely distributed among diverse human populations, constitutes a key component of the human microbiota. Members of this Gram-negative order have been shown to modulate the host immune system, play a fundamental role in the gut's microbial food webs, or be involved in pathogenesis. Bacteria inhabiting such a complex environment as the human microbiome are expected to display social behaviors and, hence, possess factors that mediate cooperative and competitive interactions.