Processing and Structure of the Lantibiotic Peptide Nso From the Human Gut Bacterium Blautia obeum A2-162 analysed by Mass Spectrometry

Gherghisan-Filip, Cristina; Saalbach, Gerhard; Hatziioanou, Diane; Narbad, Arjan; Mayer, Melinda J.

doi:10.1038/s41598-018-28248-6

Cited by 9 publications

(8 citation statements)

References 51 publications

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“…Dehydrations (−18) were present on S and T residues (Figure 6). Dehydrations on the T residue have been reported only in some nisin variants 15, 22 . Carbamido-methylations (CAM, C+57) were observed on modified cysteine residues and are an indicator of the absence of a lanthionine ring, while unmodified cysteines indicate participation in ring formation.…”

Section: Resultsmentioning

confidence: 99%

First evidence of production of the lantibiotic nisin P

García-Gutiérrez

O’Connor

Saalbach

et al. 2019

Preprint

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15Nisin P is a natural nisin variant, the genetic determinants for which were previously identified 16 in the genomes of two Streptococcus species, albeit with no confirmed evidence of production. 17 Here we describe Streptococcus agalactiae DPC7040, a human fecal isolate, which exhibits 18 antimicrobial activity against a panel of gut and food isolates by virtue of producing nisin P. 19 Nisin P was purified, and its predicted structure was confirmed by nanoLC-MS/MS, with both 20 the fully modified peptide and a variant without rings B and E being identified. Additionally, 21 we compared its spectrum of inhibition and minimum inhibitory concentration (MIC) with that 22 of nisin A and its antimicrobial effect in a fecal fermentation in comparison with nisin A and 23 H. We found that its antimicrobial activity was less potent than nisin A and H, and we propose 24 a link between this reduced activity and the peptide structure. 25 26 Keywords: nisin, antimicrobial, structure-activity relationship, fecal microbiome, 27 Structurally, nisin is classified as a lantibiotic because it contains lanthionine (Lan), an unusual 36 amino acid formed by two alanine residues linked by a sulphur atom through their β-carbon 4 . 37Other unusual amino acids present in nisin are dehydroalanine (Dha), dehydrobutyrine (Dhb) 38 3 3 and β-methyl-lanthionine 4 . Nisin activity and stability are closely related to its structure and 39 can be altered by pH changes. Increasing pH results in decreasing activity as a consequence of 40 alterations in structure, therefore, nisin is more stable at lower pH. Nisin is heat-stable and also 41 exhibits high stability at low temperatures, which makes it suitable for freeze-storage 7 . 42Nisin has nine reported natural variants ( Figure 1, Table 1). Nisin A is the most studied nisin 43 as it was the first one purified 8 . Nisin Z is considered the first natural variant of nisin A; it 44 differs in the presence of an asparagine amino acid in position 27 instead of a histidine residue 45 9 . This substitution has very little effect on antimicrobial activity, thermal and pH stability 46 compared to nisin A, but affects the solubility of the molecule, with nisin Z being more soluble 47 at neutral pH 10 . A study of its distribution also revealed that nisin Z is more widespread than 48 nisin A 10 . Nisin F, produced by L. lactis isolated from a fish gut, also has asparagine and valine 49 in positions 21 and 30 11 . Nisin Q was identified in an environmental L. lactis isolate and differs 50 from nisin A due to the presence of valine, leucine, asparagine and valine in positions 15, 21, 51 27 and 30, respectively 12 . Nisin U and U2 were the first variants found to be produced by a 52 species other than L. lactis 13 ; they are produced by Streptococcus uberis strain 42, isolated 53 from bovine mammary secretions 14 , and differ to nisin A by nine and ten amino acids, 54 respectively. Nisin H, produced by Streptococcus hyointestinalis was the first variant isolated 55 from a mammalian gastrointestin...

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Section: Resultsmentioning

confidence: 99%

First evidence of production of the lantibiotic nisin P

García-Gutiérrez

O’Connor

Saalbach

et al. 2019

Preprint

Self Cite

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“…In addition, the relative abundance of Bacteroides vulgatus (name recently changed to Phocaeicola vulgatus), which has been shown to reduce liposaccharide in the GI tract, was elevated in cats fed the FPPB or iFPPB diets [65]. Blautia obeum, which is known to produce a lantibiotic peptide, effective against multiple Clostridium species and to hydrolyze bile salts, was elevated in cats fed the FPPB or iFPPB diets [66][67][68]. In humans, Holdemanella biformis is recognized as a bacterium that reduces tumor cell proliferation and was reported to be greater in cats fed FPPB or iFPPB diets [69].…”

Section: Discussionmentioning

confidence: 99%

Dietary enrichment of resistant starches or fibers differentially alter the feline fecal microbiome and metabolite profile

Lee

Jha

et al. 2022

anim microbiome

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Background Cats are strict carnivores but possess a complex gastrointestinal (GI) microbial community that actively ferments dietary substrates that are not digested and reach the colon. The GI microbiota responses to dietary inclusion of resistant starches versus fibers have not been tested in cats. Thus, our objective was to evaluate the effects of diets enriched in resistant starch or fibers on the fecal characteristics, microbiome, and metabolite profiles of cats. Twelve healthy adult domestic shorthair cats (age = 9.6 ± 4.0 year; body weight = 3.9 ± 1.0 kg) were used in a replicated 3 × 3 Latin square design to test diets that were enriched with: (1) resistant starch (ERS), (2) a fiber-prebiotic-probiotic blend (FPPB), or (3) a fiber-prebiotic-probiotic blend + immune-modulating ingredients (iFPPB). In each 28-day period, 22 days of diet adaptation was followed by fecal and blood sample collection. Fecal samples were used for shotgun metagenomic sequencing. In addition, fecal and blood metabolite measurements and white blood cell stimulation was performed to assess immune function. Results A total of 1690 bacterial species were identified, with 259 species differing between fiber-rich and ERS treatments. In comparison with fiber-rich treatments that increased diversity and promoted Firmicutes and Bacteroidetes populations, resistant starch reduced microbial diversity and fecal pH, led to a bloom in Actinobacteria, and modified Kyoto Encyclopedia of Genes and Genomes orthology (KO) terms pertaining to starch and sucrose metabolism, fatty acid biosynthesis and metabolism, epithelial cell signaling, among others. Resistant starch also differentially modified fecal metabolite concentrations with relevance to GI and overall host health (increased butyrate; decreased propionate and protein catabolites - branched-chain fatty acids; phenols and indoles; ammonia) and reduced blood cholesterol, which correlated strongly with microbial taxa and KO terms, and allowed for a high predictive efficiency of diet groups by random forest analysis. Conclusion Even though domestic cats and other carnivores evolved by eating low-carbohydrate diets rich in protein and fat, our results demonstrate that the feline microbiome and metabolite profiles are highly responsive to dietary change and in directions that are predictable.

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“…The BGC of another nisin homologue containing four precursor genes was discovered from the dominant human gut bacterium Blautia obeum strain A2-162. Likely, the deduced products NsoA (nisin O) (Figure ) was detrimental to L. lactis MG1614, C. difficile , an urgent threat for which new antibiotics are needed, and Clostridium perfringens , the third cause of foodborne infections in the United States according to the Centers for Disease Control and Prevention (CDC). , …”

Section: Ripps Against Gram-positive Bacteriamentioning

confidence: 99%

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

Zhong

Wang

Yan

et al. 2022

ACS Bio Med Chem Au

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are of increasing interest in natural products as well as drug discovery. This empowers not only the unique chemical structures and topologies in natural products but also the excellent bioactivities such as antibacteria, antifungi, antiviruses, and so on. Advances in genomics, bioinformatics, and chemical analytics have promoted the exponential increase of RiPPs as well as the evaluation of biological activities thereof. Furthermore, benefiting from their relatively simple and conserved biosynthetic logic, RiPPs are prone to be engineered to obtain diverse analogues that exhibit distinct physiological activities and are difficult to synthesize. This Review aims to systematically address the variety of biological activities and/or the mode of mechanisms of novel RiPPs discovered in the past decade, albeit the characteristics of selective structures and biosynthetic mechanisms are briefly covered as well. Almost one-half of the cases are involved in anti-Gram-positive bacteria. Meanwhile, an increasing number of RiPPs related to anti-Gram-negative bacteria, antitumor, antivirus, etc., are also discussed in detail. Last but not least, we sum up some disciplines of the RiPPs' biological activities to guide genome mining as well as drug discovery and optimization in the future.

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Processing and Structure of the Lantibiotic Peptide Nso From the Human Gut Bacterium Blautia obeum A2-162 analysed by Mass Spectrometry

Cited by 9 publications

References 51 publications

First evidence of production of the lantibiotic nisin P

First evidence of production of the lantibiotic nisin P

Dietary enrichment of resistant starches or fibers differentially alter the feline fecal microbiome and metabolite profile

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

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