A widespread family of ribosomal peptide metallophores involved in bacterial adaptation to metal stress.

Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a structurally diverse group of natural products that bacteria employ in their survival strategies. Herein, we characterized the structure, the biosynthetic pathway, and the mode of action of a RiPP family called bufferins. With thousands of homologous biosynthetic gene clusters throughout the bacterial phylogenetic tree, bufferins form by far the largest family of RiPPs modified by multinuclear nonheme iron-dependent oxidases (MNIO, DUF692 family).

Exploring the genetic basis of natural resistance to microcins.

produce an arsenal of antimicrobial compounds including microcins, ribosomally produced antimicrobial peptides showing diverse structures and mechanisms of action. Microcins target close relatives of the producing strain to promote its survival. Their narrow spectrum of antibacterial activity makes them a promising alternative to conventional antibiotics, as it should decrease the probability of resistance dissemination and collateral damage to the host's microbiota.

The pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide.

Covering: 1992 up to 2023Since their discovery, lasso peptides went from peculiarities to be recognized as a major family of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products that were shown to be spread throughout the bacterial kingdom. Microcin J25 was first described in 1992, making it one of the earliest known lasso peptides. No other lasso peptide has since then been studied to such an extent as microcin J25, yet, previous review articles merely skimmed over all the research done on this exceptional lasso peptide.

The name of the game: palaeoproteomics and radiocarbon dates further refine the presence and dispersal of caprines in eastern and southern Africa.

We report the first large-scale palaeoproteomics research on eastern and southern African zooarchaeological samples, thereby refining our understanding of early caprine (sheep and goat) pastoralism in Africa. Assessing caprine introductions is a complicated task because of their skeletal similarity to endemic wild bovid species and the sparse and fragmentary state of relevant archaeological remains. Palaeoproteomics has previously proved effective in clarifying species attributions in African zooarchaeological materials, but few comparative protein sequences of wild bovid species have been available.

Molecular acclimation of to halite brine inclusions.

Halophilic microorganisms have long been known to survive within the brine inclusions of salt crystals, as evidenced by the change in color for salt crystals containing pigmented halophiles. However, the molecular mechanisms allowing this survival has remained an open question for decades. While protocols for the surface sterilization of halite (NaCl) have enabled isolation of cells and DNA from within halite brine inclusions, "-omics" based approaches have faced two main technical challenges: (1) removal of all contaminating organic biomolecules (including proteins) from halite surfaces, and (2) performing selective biomolecule extractions directly from cells contained within halite brine inclusions with sufficient speed to avoid modifications in gene expression during extraction.

Impact of microcin J25 on the porcine microbiome in a continuous culture model.

The increased prevalence of spp. resistance in swine spurs the search for alternatives to antibiotics. Microcin J25 (MccJ25), a bacteriocin produced by , is a potent inhibitor of several pathogenic bacteria including .

Evaluating the Potential and Synergetic Effects of Microcins against Multidrug-Resistant .

The advent of multidrug-resistant bacteria has hampered the development of new antibiotics, exacerbating their morbidity and mortality. In this context, the gastrointestinal tract reveals a valuable source of novel antimicrobials. Microcins are bacteriocins produced by members of the family which are endowed with a wide diversity of structures and mechanisms of action, and exert potent antibacterial activity against closely related bacteria.

Effects of drinking water supplementation with Lactobacillus reuteri, and a mixture of reuterin and microcin J25 on the growth performance, caecal microbiota and selected metabolites of broiler chickens.

Background: Since the overuse of antibiotics in animal production has led to a selection of antibiotic-resistant pathogens that affect humans and animals as well. Scientists are therefore searching for novel natural alternatives to antibiotics. In this study Lactobacillus reuteri and a combination of reuterin and microcin J25 (RJ) were evaluated as promoters of growth and modulators of the cecal microbiota and metabolite profiles in broiler chickens.

Gastrointestinal Stability and Cytotoxicity of Bacteriocins From Gram-Positive and Gram-Negative Bacteria: A Comparative Study.

Bacteriocins are receiving increased attention as potent candidates in food preservation and medicine. Although the inhibitory activity of bacteriocins has been studied widely, little is known about their gastrointestinal stability and toxicity toward normal human cell lines. The aim of this study was to evaluate the gastrointestinal stability and activity of microcin J25, pediocin PA-1, bactofencin A and nisin using models.

Bacteriocins to Thwart Bacterial Resistance in Gram Negative Bacteria.

An overuse of antibiotics both in human and animal health and as growth promoters in farming practices has increased the prevalence of antibiotic resistance in bacteria. Antibiotic resistant and multi-resistant bacteria are now considered a major and increasing threat by national health agencies, making the need for novel strategies to fight bugs and super bugs a first priority. In particular, Gram-negative bacteria are responsible for a high proportion of nosocomial infections attributable for a large part to , such as pathogenic , , and .

Untangling the fibre ball: Proteomic characterization of South American camelid hair fibres by untargeted multivariate analysis and molecular networking.

The proteomic analysis of hairs, yarns or textiles has emerged as a powerful method to determine species of origin, mainly used in archaeozoological research and fraud control. Differentiation between the South American camelid (SAC) species (the wild guanaco and vicuña and their respective domesticates the llama and alpaca) is particularly challenging due to poor database information and significant hybridization between species. In this study, we analysed 41 modern and 4 archaeological samples from the four SACs species.

Palaeoproteomics gives new insight into early southern African pastoralism.

The advent of domestication is a major step that transformed the subsistence strategies of past human societies. In Africa, domestic caprines (sheep and goat) were introduced in the north-eastern part of the continent from the Near East more than 9000 years ago. However, their diffusion southwards was slow.

Microcin J25 Exhibits Inhibitory Activity Against Newport in Continuous Fermentation Model Mimicking Swine Colonic Conditions.

Microcin J25 (MccJ25), a 21-amino acid bacteriocin produced by (), is a potent inhibitor of Enterobacteriaceae, including pathogenic , , and . Its lasso structure makes it highly stable and therefore of interest as a possible antimicrobial agent in foods or as an alternative to antibiotics in livestock production. In the present study, we aimed to evaluate the inhibitory activity of MccJ25 against subsp.

Phenomic and genomic approaches to studying the inhibition of multiresistant Salmonella enterica by microcin J25.

In livestock production, antibiotics are used to promote animal growth, control infections and thereby increase profitability. This practice has led to the emergence of multiresistant bacteria such as Salmonella, of which some serovars are disseminated in the environment. The objective of this study is to evaluate microcin J25 as an inhibitor of Salmonella enterica serovars of various origins including human, livestock and food.

Time resolved transient circular dichroism spectroscopy using synchrotron natural polarization.

Ultraviolet (UV) synchrotron radiation circular dichroism (SRCD) spectroscopy has made an important contribution to the determination and understanding of the structure of bio-molecules. In this paper, we report an innovative approach that we term time-resolved SRCD (tr-SRCD), which overcomes the limitations of current broadband UV SRCD setups. This technique allows accessing ultrafast time scales (down to nanoseconds), previously measurable only by other methods, such as infrared (IR), nuclear magnetic resonance (NMR), fluorescence and absorbance spectroscopies, and small angle X-ray scattering (SAXS).

Complete Genome Sequences of Four Strains Isolated from Metal- and Radionuclide-Rich Soils.

Here, we present the genome sequences of four strains, which were isolated at different locations in Europe from metal- or radionuclide-rich soils. High-quality complete genome sequences were obtained with PacBio and Illumina data sets with an original two-step procedure.

Evidence of Cis/Trans-Isomerization at Pro7/Pro16 in the Lasso Peptide Microcin J25.

Microcin J25 is a ribosomal synthesized and post-translationally modified peptide (RiPP) characterized by a mechanically interlocked topology called the lasso fold. This structure provides microcin J25 a potent antimicrobial activity resulting from internalization via the siderophore receptor FhuA and further inhibition of the RNA polymerase. In the present work, nuclear magnetic resonance (NMR) and trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) were used to investigate the lasso structure of microcin J25.

Binding Specificity of Native Odorant-Binding Protein Isoforms Is Driven by Phosphorylation and -N-Acetylglucosaminylation in the Pig .

Odorant-binding proteins (OBP) are secreted in the nasal mucus at the vicinity of olfactory receptors (ORs). They act, at least, as an interface between hydrophobic and volatile odorant molecules and the hydrophilic medium bathing the ORs. They have also been hypothesized to be part of the molecular coding of odors and pheromones, by forming specific complexes with odorant molecules that could ultimately stimulate ORs to trigger the olfactory transduction cascade.

Structural signatures of the class III lasso peptide BI-32169 and the branched-cyclic topoisomers using trapped ion mobility spectrometry-mass spectrometry and tandem mass spectrometry.

Lasso peptides are a class of bioactive ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by a mechanically interlocked topology, where the C-terminal tail of the peptide is threaded and trapped within an N-terminal macrolactam ring. BI-32169 is a class III lasso peptide containing one disulfide bond that further stabilizes the lasso structure. In contrast to its branched-cyclic analog, BI-32169 has higher stability and is known to exert a potent inhibitory activity against the human glucagon receptor.

Novel Mechanism for Surface Layer Shedding and Regenerating in Bacteria Exposed to Metal-Contaminated Conditions.

Surface layers (S-layers) are components of the cell walls throughout the Bacteria and the Archaea that provide protection for microorganisms against diverse environmental stresses, including metal stress. We have previously characterized the process by which S-layers serve as a nucleation site for metal mineralization in an archaeon for which the S-layer represents the only cell wall component. Here, we test the hypothesis originally proposed in cyanobacteria that a "shedding" mechanism exists for replacing S-layers that have become mineral-encrusted, using sp.

Fate and Biological Activity of the Antimicrobial Lasso Peptide Microcin J25 Under Gastrointestinal Tract Conditions.

The bacteriocin microcin J25 (MccJ25) inhibits the growth of Gram-negative pathogens including and species, and . This 21-amino acid peptide has remarkable stability to heat and extreme pH values and resistance to many proteases, thanks to a characteristic lasso structure. In this study, we used the dynamic simulator TIM-1 as gastro-intestinal tract model to evaluate the stability and antibacterial activity of MccJ25 during passage through the proximal portion of the human gastrointestinal tract.

Synthesis, antimicrobial activity and conformational analysis of the class IIa bacteriocin pediocin PA-1 and analogs thereof.

The antimicrobial peptide pediocin PA-1 is a class IIa bacteriocin that inhibits several clinically relevant pathogens including Listeria spp. Here we report the synthesis and characterization of whole pediocin PA-1 and novel analogs thereof using a combination of solid- and solution-phase strategies to overcome difficulties due to instability and undesired reactions. Pediocin PA-1 thus synthesized was a potent inhibitor of Listeria monocytogenes (MIC = 6.

An orthogonal system for heterologous expression of actinobacterial lasso peptides in Streptomyces hosts.

Lasso peptides are ribosomally synthesized and post-translationally modified peptides produced by bacteria. They are characterized by an unusual lariat-knot structure. Targeted genome scanning revealed a wide diversity of lasso peptides encoded in actinobacterial genomes, but cloning and heterologous expression of these clusters turned out to be problematic.

Structural Basis for Natural Product Selection and Export by Bacterial ABC Transporters.

Bacteria under stress produce ribosomally synthesized and post-translationally modified peptides (RiPPs) to target closely related species, such as the lasso peptide microcin J25 (MccJ25). These peptides are also toxic to the producing organisms that utilize dedicated ABC transporters to achieve self-immunity. MccJ25 is exported by the Escherichia coli ABC transporter McjD through a complex mechanism of recognition that has remained elusive.

Metal ions induced secondary structure rearrangements: mechanically interlocked lasso vs. unthreaded branched-cyclic topoisomers.

Metal ions can play a significant role in a variety of important functions in protein systems including cofactor for catalysis, protein folding, assembly, structural stability and conformational change. In the present work, we examined the influence of alkali (Na, K and Cs), alkaline earth (Mg and Ca) and transition (Co, Ni and Zn) metal ions on the conformational space and analytical separation of mechanically interlocked lasso peptides. Syanodin I, sphingonodin I, caulonodin III and microcin J25, selected as models of lasso peptides, and their respective branched-cyclic topoisomers were submitted to native nESI trapped ion mobility spectrometry-mass spectrometry (TIMS-MS).