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Structural Basis of the Mechanisms of Action and Immunity of Lactococcin A, a Class IId Bacteriocin.Applied and Environmental Microbiology Mar 2023Lactococcin A (LcnA), a class IId bacteriocin, induces membrane leakage and cell death by specifically binding to the membrane receptor-mannose phosphotransferase system...
Lactococcin A (LcnA), a class IId bacteriocin, induces membrane leakage and cell death by specifically binding to the membrane receptor-mannose phosphotransferase system (man-PTS), as is the case for pediocin-like (class IIa) bacteriocins. The cognate immunity protein of bacteriocins, which protects the producer cell from its own bacteriocin, recognizes and binds to the bacteriocin-man-PTS complex, consequently blocking membrane leakage. We previously deciphered the mode of action and immunity of class IIa bacteriocins. Here, we determined the structure of the ternary complex of LcnA, LciA (, the immunity protein), and its receptor, , the man-PTS of Lactococcus lactis (ll-man-PTS). An external loop on the membrane-located component IIC of ll-man-PTS was found to prevent specific binding of the N-terminal region of LcnA to the site recognized by pediocin-like bacteriocins. Thus, the N-terminal β-sheet region of LcnA recognized an adjacent site on the extracellular side of ll-man-PTS, with the LcnA C-terminal hydrophobic helix penetrating into the membrane. The cytoplasmic cleft formed within the man-PTS Core and Vmotif domains induced by embedded LcnA from the periplasmic side is adopted by the appropriate angle between helices H3 and H4 of the N terminus of LciA. The flexible C terminus of LciA then blocks membrane leakage. To summarize, our findings reveal the molecular mechanisms of action and immunity of LcnA and LciA, laying a foundation for further design of class IId bacteriocins. Class IId (lactococcin-like) bacteriocins and class IIa (pediocin-like) bacteriocins share a few similarities: (i) both induce membrane leakage and cell death by specifically binding the mannose phosphotransferase system (man-PTS) on their target cells, and (ii) cognate immunity proteins recognize and bind to the bacteriocin-man-PTS complex to block membrane leakage. However, class IId bacteriocins lack the "pediocin box" motif, which is typical of class IIa bacteriocins, and basically target only lactococcal cells; in contrast, class IIa bacteriocins target diverse bacterial cells, but not lactococcal cells. We previously solved the structure of class IIa bacteriocin-receptor-immunity ternary complex from Lactobacillus sakei. Here, we determined the structure of the ternary complex of class IId bacteriocin LcnA, its cognate immunity protein LciA, and its receptor, the man-PTS of Lactococcus lactis. By comparing the interactions between man-PTS and class IIa and class IId bacteriocins, this study affords some clues to better understand the specificity of bacteriocins targeting the mannose phosphotransferase system.
Topics: Pediocins; Mannose; Bacteriocins; Lactococcus lactis; Phosphotransferases
PubMed: 36840592
DOI: 10.1128/aem.00066-23 -
BMC Bioinformatics Jan 2023Bacteriocins are defined as thermolabile peptides produced by bacteria with biological activity against taxonomically related species. These antimicrobial peptides have...
BACKGROUND
Bacteriocins are defined as thermolabile peptides produced by bacteria with biological activity against taxonomically related species. These antimicrobial peptides have a wide application including disease treatment, food conservation, and probiotics. However, even with a large industrial and biotechnological application potential, these peptides are still poorly studied and explored. BADASS is software with a user-friendly graphical interface applied to the search and analysis of bacteriocin diversity in whole-metagenome shotgun sequencing data.
RESULTS
The search for bacteriocin sequences is performed with tools such as BLAST or DIAMOND using the BAGEL4 database as a reference. The putative bacteriocin sequences identified are used to determine the abundance and richness of the three classes of bacteriocins. Abundance is calculated by comparing the reads identified as bacteriocins to the reads identified as 16S rRNA gene using SILVA database as a reference. BADASS has a complete pipeline that starts with the quality assessment of the raw data. At the end of the analysis, BADASS generates several plots of richness and abundance automatically as well as tabular files containing information about the main bacteriocins detected. The user is able to change the main parameters of the analysis in the graphical interface. To demonstrate how the software works, we used four datasets from WMS studies using default parameters. Lantibiotics were the most abundant bacteriocins in the four datasets. This class of bacteriocin is commonly produced by Streptomyces sp.
CONCLUSIONS
With a user-friendly graphical interface and a complete pipeline, BADASS proved to be a powerful tool for prospecting bacteriocin sequences in Whole-Metagenome Shotgun Sequencing (WMS) data. This tool is publicly available at https://sourceforge.net/projects/badass/ .
Topics: Bacteriocins; RNA, Ribosomal, 16S; Software; Bacteria; Metagenome; Anti-Bacterial Agents
PubMed: 36670373
DOI: 10.1186/s12859-022-05106-x -
Microbiology Spectrum Jun 2023Klebsiella pneumoniae produces several kinds of bacteriocins that have antimicrobial effects against closely related species, but few studies have comprehensively...
Klebsiella pneumoniae produces several kinds of bacteriocins that have antimicrobial effects against closely related species, but few studies have comprehensively reported bacteriocin distribution among the Klebsiella population. In this study, we identified bacteriocin genes in 180 K. pneumoniae species complex genomes, including 170 hypermucoviscous isolates, and investigated the antibacterial activity against 50 strains, including antimicrobial-resistant organisms, belonging to multiple species, namely, Klebsiella spp., Escherichia coli, Pseudomonas spp., Acinetobacter spp., Enterobacter cloacae, Stenotrophomonas maltophilia, Chryseobacterium indologenes, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans. Our study determined that 32.8% (59/180) of isolates carried at least one bacteriocin type. Different types of bacteriocin were usually present in different specific sequence types (STs); meanwhile, bacteriocins were not detected in certain STs. Microcin E492 was the most prevalent bacteriocin (14.4%), mostly in ST23 isolates, and displayed a wide spectrum of activity, including against Klebsiella spp., E. coli, Pseudomonas spp., and Acinetobacter spp. Cloacin-like bacteriocin was detected in 7.2% of strains, all of which were non-ST23 isolates, and exhibited inhibitory activity against closely related species, mainly Klebsiella spp. Klebicin B-like bacteriocin was detected at a rate of 9.4%, although 82.4% of these strains carried a disrupted bacteriocin gene, and an inhibitory effect could not be observed from the intact-gene-carrying isolates. Other bacteriocins, such as microcin S-like, microcin B17, and klebicin C-like, were detected at lower rates and had limited inhibitory activity. Our findings suggested that Klebsiella strains that carry different bacteriocin types may affect the composition of the surrounding bacterial community. Klebsiella pneumoniae is a Gram-negative commensal bacterium that asymptomatically colonizes human mucosal membranes, such as the intestinal tract, but it is also a leading cause of health care- and community-associated infections. Additionally, multidrug-resistant K. pneumoniae has been continuously evolving, which significantly challenges the available chemotherapeutic treatment for its infections. K. pneumoniae produces several kinds of antimicrobial peptides known as bacteriocins, which have antibacterial activity against closely related species. This work was the first comprehensive report of bacteriocin distribution among the hypermucoviscous K. pneumoniae species complex population and the inhibitory activity of each bacteriocin type against various species, including multidrug-resistant strains. Our findings provide a foundation for future studies on the K. pneumoniae species complex, including studies on the competition within the microflora and the potential applications of bacteriocins in treating multidrug-resistant bacteria.
Topics: Humans; Klebsiella; Klebsiella pneumoniae; Escherichia coli; Bacteriocins; Anti-Bacterial Agents; Gram-Negative Bacteria; Microbial Sensitivity Tests
PubMed: 37154746
DOI: 10.1128/spectrum.00863-23 -
Current Topics in Medicinal Chemistry 2015With the growing concerns in the scientific and health communities over increasing levels of antibiotic resistance, antimicrobial peptide bacteriocins have emerged as... (Review)
Review
With the growing concerns in the scientific and health communities over increasing levels of antibiotic resistance, antimicrobial peptide bacteriocins have emerged as promising alternatives to conventional small molecule antibiotics. A substantial attention has recently focused on the utilization of bacteriocins in food preservation and health safety. Despite the fact that a large number of bacteriocins have been reported, only a few have been fully characterized and structurally elucidated. Since knowledge of the molecular structure is a key for understanding the mechanism of action and therapeutic effects of peptide, we centered our focus in this review on the structure-activity relationships of bacteriocins with a particular focus in seven bacteriocins, namely, nisin, microcin J25, microcin B17, microcin C, leucocin A, sakacin P, and pediocin PA-1. Significant structural changes responsible for the altered activity of the recent bacteriocin analogues are discussed here.
Topics: Anti-Bacterial Agents; Bacteriocins; Humans; Structure-Activity Relationship
PubMed: 26265354
DOI: 10.2174/1568026615666150812121103 -
Applied and Environmental Microbiology Jan 2012Bacteriocins are an abundant and diverse group of ribosomally synthesized antimicrobial peptides produced by bacteria and archaea. Traditionally, bacteriocin production... (Review)
Review
Bacteriocins are an abundant and diverse group of ribosomally synthesized antimicrobial peptides produced by bacteria and archaea. Traditionally, bacteriocin production has been considered an important trait in the selection of probiotic strains, but until recently, few studies have definitively demonstrated the impact of bacteriocin production on the ability of a strain to compete within complex microbial communities and/or positively influence the health of the host. Although research in this area is still in its infancy, there is intriguing evidence to suggest that bacteriocins may function in a number of ways within the gastrointestinal tract. Bacteriocins may facilitate the introduction of a producer into an established niche, directly inhibit the invasion of competing strains or pathogens, or modulate the composition of the microbiota and influence the host immune system. Here we review the role of bacteriocin production in complex microbial communities and their potential to enhance human health.
Topics: Animals; Bacteriocins; Humans; Intestinal Mucosa; Microbial Consortia; Microbial Interactions; Probiotics; Signal Transduction
PubMed: 22038602
DOI: 10.1128/AEM.05576-11 -
Microbial Biotechnology Sep 2022Pseudomonas sp. strain 166 was isolated from soil samples from Changbai Mountains. A novel bacteriocin PA166 from Pseudomonas sp. 166 was purified using ammonium...
Pseudomonas sp. strain 166 was isolated from soil samples from Changbai Mountains. A novel bacteriocin PA166 from Pseudomonas sp. 166 was purified using ammonium sulfate, dextran gel chromatography column and Q-Sepharose column chromatography successively. The molecular mass of bacteriocin PA166 was found to be 49.38 kDa by SDS-PAGE and liquid chromatography-mass spectrometry (MS)/MS. Bacteriocin PA166 showed stability at a wide range of pH (2-10), and thermal stability (40, 60, 80 and 100°C). The bacteriocin PA166 antimicrobial activity was slightly inhibited by Ca , K and Mg . The minimum bactericidal concentrations of bacteriocin PA166 against five Pasteurella multocida strains ranged from 2 to 8 μg ml . Bacteriocin PA166 showed low cytotoxicity and a higher treatment index (TI = 82.51). Fluorescence spectroscopy indicated that bacteriocin PA166 destroyed the cell membrane to exert antimicrobial activity. In summary, bacteriocin PA166 had strong antibacterial activity, high TI and low toxicity, and hence could serve as a potential clinical therapeutic drug.
Topics: Anti-Bacterial Agents; Bacteriocins; Electrophoresis, Polyacrylamide Gel; Molecular Weight; Pseudomonas
PubMed: 35849816
DOI: 10.1111/1751-7915.14096 -
Scientific Reports Jun 2021Streptococcus mutans produces bacteriocins that show antibacterial activity against several bacteria. However, comprehensive analysis of these bacteriocins has not been...
Streptococcus mutans produces bacteriocins that show antibacterial activity against several bacteria. However, comprehensive analysis of these bacteriocins has not been well done. In this study, we isolated 125 S. mutans strains from volunteers and determined their whole genome sequence. Based on the genome analysis, the distribution of each bacteriocin gene (mutacins I-IV, K8 and Smb) was investigated. We found 17, 5, and 2 strains showing 100% matches with mutacin I, mutacin II and mutacin III, respectively. Five mutacin III-positive strains had 2 mismatches compared to mature mutacin III. In 67 mutacin IV-positive strains, 38 strains showed 100% match with mutacin IV, while 29 strains showed some variations. In 23 mutacin K8- and 32 mutacin Smb-positive strains, all except one mutacin K8-positive strain showed 100% match with the mature peptides. Among 125 strains, 84 (65.1%), 26 (20.2%), and 5 (3.9%) strains were positive for one, two and three bacteriocin genes, respectively. Then, the antibacterial activity against oral streptococci and other oral bacterial species was investigated by using bacteriocin gene single-positive strains. Each bacteriocin gene-positive strain showed a different pattern of antibacterial activity. These results speculate that individual S. mutans strains may affect the bacterial composition of dental plaques.
Topics: Amino Acid Sequence; Anti-Bacterial Agents; Antibiosis; Bacteriocins; Gene Expression Regulation, Bacterial; Humans; Microbial Sensitivity Tests; Mutation; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Streptococcus mutans
PubMed: 34155274
DOI: 10.1038/s41598-021-92370-1 -
Polish Journal of Microbiology 2013Bacteriocines are small peptides with anti-bacterial properties. They are produced both by Gram-positive and Gram-negative bacteria. Until now, a few hundred... (Review)
Review
Bacteriocines are small peptides with anti-bacterial properties. They are produced both by Gram-positive and Gram-negative bacteria. Until now, a few hundred bacteriocines were described. Classification of bacteriocines undergoes continuous alterations, as new developments regarding their structure, amino acid sequence and recognised mechanism of their action are available. Some of bacteriocins (lantibiotics) contain atypical amino acids, such as lantionine (Lan), methyllantionine (MeLan), dehydroalanine (Dha), dehydrobutyrine (Dhb), or D-alanine (D-Ala). The best recognized bacteriocines are produced by lactic acid bacteria, including nisine produced by strains of Lactococcus lactis. These bacteriocines have been recognized to be fully safe for humans. At present, nisine is used in food industry, as a preserving agent. Other lactic acid bacteria bacteriocines and probiotic preparations provide an alternative for antibiotics, and are used in food and in animal feed.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacteriocins; Humans; Protein Structure, Secondary
PubMed: 24459827
DOI: No ID Found -
Journal of Microbiology and... Sep 2019Acetic acid is indirectly involved in cell center metabolism, and acetic acid metabolism is the core of central metabolism, affecting and regulating the production of... (Review)
Review
Acetic acid is indirectly involved in cell center metabolism, and acetic acid metabolism is the core of central metabolism, affecting and regulating the production of bacteriocin. Bacteriocin is a natural food preservative that has been used in the meat and dairy industries and winemaking. In this paper, the effects of acetic acid on bacteriocin produced by Gram-positive bacteria were reviewed. It was found that acetic acid in the undissociated state can diffuse freely through the hydrophobic layer of the membrane and dissociate, affecting the production, yield, and activity of bacteriocin. In particular, the effect of acetic acid on cell membranes is summarized. The link between acetic acid metabolism, quorum sensing, and bacteriocin production mechanisms is also highlighted.
Topics: Acetic Acid; Anti-Bacterial Agents; Bacteriocins; Cell Membrane; Food Preservatives; Gram-Positive Bacteria; Plasmids; Quorum Sensing
PubMed: 31336430
DOI: 10.4014/jmb.1905.05060 -
International Journal of Environmental... Oct 2020Bacteriocins are antimicrobial peptides some of which are endowed with antiviral, anticancer and antibiofilm properties. These properties could be improved through... (Review)
Review
Bacteriocins are antimicrobial peptides some of which are endowed with antiviral, anticancer and antibiofilm properties. These properties could be improved through synergistic interactions of these bacteriocins with other bioactive molecules such as antibiotics, phages, nanoparticles and essential oils. A number of studies are steadily reporting the effects of these combinations as new and potential therapeutic strategies in the future, as they may offer many incentives over existing therapies. In particular, bacteriocins can benefit from combination with nanoparticles which can improve their stability and solubility, and protect them from enzymatic degradation, reduce their interactions with other molecules and improve their bioavailability. Furthermore, the combination of bacteriocins with other antimicrobials is foreseen as a way to reduce the development of antibiotic resistance due to the involvement of several modes of action. Another relevant advantage of these synergistic combinations is that it decreases the concentration of each antimicrobial component, thereby reducing their side effects such as their toxicity. In addition, combination can extend the utility of bacteriocins as antiviral or anticancer agents. Thus, in this review, we report and discuss the synergistic effects of bacteriocin combinations as medicines, and also for other diverse applications including, antiviral, antispoilage, anticancer and antibiofilms.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteriocins
PubMed: 33114656
DOI: 10.3390/ijerph17217835