New type non-lantibiotic bacteriocins: circular and leaderless bacteriocins

Bacteriocins are antimicrobial peptides that are ribosomally synthesised by bacteria. Bacteriocins produced by Gram-positive bacteria, including lactic acid bacteria, are under focus as the next generation of safe natural biopreservatives and as therapeutic alternatives to antibiotics. Recently, two novel types of non-lantibiotic class II bacteriocins have been reported with unique characteristics in their structure and biosynthesis mechanism. One is a circular bacteriocin that contains a head-to-tail structure in the mature form, and the other is a leaderless bacteriocin without an N-terminal extension in the precursor peptide. A circular structure can provide the peptide with remarkable stability against various stresses; indeed, circular bacteriocins are known to possess higher stability than general linear bacteriocins. Leaderless bacteriocins are distinct from general bacteriocins, because they do not contain N-terminal leader sequences, which are responsible for the recognition process during secretion and for inactivation of bacteriocins inside producer cells. Leaderless bacteriocins do not require any post-translational processing for activity. These two novel types of bacteriocins are promising antimicrobial compounds, and their biosynthetic mechanisms are expected to be applied in synthetic biology to design new peptides and for new mass production systems. However, many questions remain about their biosynthesis. In this review, we introduce recent studies on these types of bacteriocins and their potential to open a new world of antimicrobial peptides.

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Expression of Anti-Lipopolysaccharide Factor Isoform 3 in Chlamydomonas reinhardtii Showing High Antimicrobial Activity

Marine Drugs ◽

10.3390/md19050239 ◽

2021 ◽

Vol 19 (5) ◽

pp. 239

Author(s):

Anguo Li ◽

Ruihao Huang ◽

Chaogang Wang ◽

Qunju Hu ◽

Hui Li ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Antimicrobial Peptide ◽

Chlamydomonas Reinhardtii ◽

Penaeus Monodon ◽

Total Soluble Protein ◽

Cell Factory ◽

Gram Positive Bacteria ◽

Resistance Selection ◽

Expression Cluster ◽

Potential Strategy

Antimicrobial peptides are a class of proteins with antibacterial functions. In this study, the anti-lipopolysaccharide factor isoform 3 gene (ALFPm3), encoding an antimicrobial peptide from Penaeus monodon with a super activity was expressed in Chlamydomonas reinhardtii, which would develop a microalga strain that can be used for the antimicrobial peptide production. To construct the expression cluster, namely pH2A-Pm3, the codon optimized ALFPm3 gene was fused with the ble reporter by 2A peptide and inserted into pH124 vector. The glass-bead method was performed to transform pH2A-Pm3 into C. reinhardtii CC-849. In addition to 8 μg/mL zeocin resistance selection, the C. reinhardtii transformants were further confirmed by genomic PCR and RT-PCR. Western blot analysis showed that the C. reinhardtii-derived ALFPm3 (cALFPm3) was successfully expressed in C. reinhardtii transformants and accounted for 0.35% of the total soluble protein (TSP). Furthermore, the results of antibacterial assay revealed that the cALFPm3 could significantly inhibit the growth of a variety of bacteria, including both Gram-negative bacteria and Gram-positive bacteria at a concentration of 0.77 μM. Especially, the inhibition could last longer than 24 h, which performed better than ampicillin. Hence, this study successfully developed a transgenic C. reinhardtii strain, which can produce the active ALFPm3 driven from P. monodon, providing a potential strategy to use C. reinhardtii as the cell factory to produce antimicrobial peptides.

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Plant antimicrobial peptides: structures, functions, and applications

Botanical Studies ◽

10.1186/s40529-021-00312-x ◽

2021 ◽

Vol 62 (1) ◽

Author(s):

Junpeng Li ◽

Shuping Hu ◽

Wei Jian ◽

Chengjian Xie ◽

Xingyong Yang

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Agricultural Production ◽

Food Additives ◽

Antimicrobial Activities ◽

Gram Positive Bacteria ◽

Potential Applications ◽

Potential Applicability ◽

Bacteria And Fungi ◽

Positively Charged

AbstractAntimicrobial peptides (AMPs) are a class of short, usually positively charged polypeptides that exist in humans, animals, and plants. Considering the increasing number of drug-resistant pathogens, the antimicrobial activity of AMPs has attracted much attention. AMPs with broad-spectrum antimicrobial activity against many gram-positive bacteria, gram-negative bacteria, and fungi are an important defensive barrier against pathogens for many organisms. With continuing research, many other physiological functions of plant AMPs have been found in addition to their antimicrobial roles, such as regulating plant growth and development and treating many diseases with high efficacy. The potential applicability of plant AMPs in agricultural production, as food additives and disease treatments, has garnered much interest. This review focuses on the types of plant AMPs, their mechanisms of action, the parameters affecting the antimicrobial activities of AMPs, and their potential applications in agricultural production, the food industry, breeding industry, and medical field.

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Maturation pathway of nisin and other lantibiotics: post-translationally modified antimicrobial peptides exported by Gram-positive bacteria

Molecular Microbiology ◽

10.1111/j.1365-2958.1995.mmi_17030427.x ◽

1995 ◽

Vol 17 (3) ◽

pp. 427-437 ◽

Cited By ~ 126

Author(s):

Willem M. de Vos ◽

Oscar P. Kuipers ◽

Jan Roelof van der Meer ◽

Roland J. Siezen

Keyword(s):

Antimicrobial Peptides ◽

Gram Positive ◽

Gram Positive Bacteria

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Characterization of Leader Processing Shows That Partially Processed Mersacidin Is Activated by AprE After Export

Frontiers in Microbiology ◽

10.3389/fmicb.2021.765659 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jakob H. Viel ◽

Amanda Y. van Tilburg ◽

Oscar P. Kuipers

Keyword(s):

Antimicrobial Activity ◽

Synthetic Biology ◽

Heterologous Expression ◽

Expression System ◽

Heterologous Expression System ◽

Proteolytic Activation ◽

E Coli ◽

Gram Positive Bacteria ◽

Precursor Peptide ◽

Potential Applications

The ribosomally synthesized and post-translationally modified peptide mersacidin is a class II lanthipeptide with good activity against Gram-positive bacteria. The intramolecular lanthionine rings, that give mersacidin its stability and antimicrobial activity, are specific structures with potential applications in synthetic biology. To add the mersacidin modification enzymes to the synthetic biology toolbox, a heterologous expression system for mersacidin in Escherichia coli has recently been developed. While this system was able to produce fully modified mersacidin precursor peptide that could be activated by Bacillus amyloliquefaciens supernatant and showed that mersacidin was activated in an additional proteolytic step after transportation out of the cell, it lacked a mechanism for clean and straightforward leader processing. Here, the protease responsible for activating mersacidin was identified and heterologously produced in E. coli, improving the previously reported heterologous expression system. By screening multiple proteases, the stringency of proteolytic activity directly next to a very small lanthionine ring is demonstrated, and the full two-step proteolytic activation of mersacidin was elucidated. Additionally, the effect of partial leader processing on diffusion and antimicrobial activity is assessed, shedding light on the function of two-step leader processing.

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The Process Capability Matrix: A Tool for Manufacturing Variation Analysis at the Systems Level

Volume 4: Design for Manufacturing Conference ◽

10.1115/detc97/dfm-4348 ◽

1997 ◽

Author(s):

Daniel D. Frey ◽

Kevin N. Otto

Keyword(s):

Production Systems ◽

Feedforward Control ◽

Control Strategies ◽

Block Diagram ◽

Process Capability ◽

Statistical Correlation ◽

Design Decision ◽

Variation Reduction ◽

The Matrix ◽

New Type

Abstract This paper introduces the concept of a process capability matrix — an ordered set of dimensionless parameters that capture information on a manufacturing system’s response to noises. The matrix captures information on the magnitude of noise, sensitivity to noise, and tolerance to variation. Algorithms and equations are presented that use the matrix to compute the yield of a manufacturing system. The method proves to be accurate on real engineering problems for which existing techniques are inadequate due to statistical correlation among product acceptance criteria. The process capability matrix also proves useful in a new type of block diagram of production systems. The block diagrams are shown to be useful in evaluating the effectiveness of feedforward control strategies for variation reduction. An electronics assembly process serves as an example of the algorithms and their use in design decision making.

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Cranberry Polyphenols and Prevention against Urinary Tract Infections: Relevant Considerations

Molecules ◽

10.3390/molecules25153523 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3523 ◽

Cited By ~ 4

Author(s):

Dolores González de Llano ◽

M. Victoria Moreno-Arribas ◽

Begoña Bartolomé

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Protective Effects ◽

Current Effort ◽

Beneficial Effects ◽

Gram Positive Bacteria ◽

Etiological Agents ◽

New Research ◽

Tract Infections ◽

Therapeutic Alternatives

Cranberry (Vaccinium macrocarpon) is a distinctive source of polyphenols as flavonoids and phenolic acids that has been described to display beneficial effects against urinary tract infections (UTIs), the second most common type of infections worldwide. UTIs can lead to significant morbidity, especially in healthy females due to high rates of recurrence and antibiotic resistance. Strategies and therapeutic alternatives to antibiotics for prophylaxis and treatment against UTIs are continuously being sought after. Different to cranberry, which have been widely recommended in traditional medicine for UTIs prophylaxis, probiotics have emerged as a new alternative to the use of antibiotics against these infections and are the subject of new research in this area. Besides uropathogenic Escherichia coli (UPEC), the most common bacteria causing uncomplicated UTIs, other etiological agents, such as Klebsiellapneumoniae or Gram-positive bacteria of Enterococcus and Staphylococcus genera, seem to be more widespread than previously appreciated. Considerable current effort is also devoted to the still-unraveled mechanisms that are behind the UTI-protective effects of cranberry, probiotics and their new combined formulations. All these current topics in the understanding of the protective effects of cranberry against UTIs are reviewed in this paper. Further progresses expected in the coming years in these fields are also discussed.

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A Rapid Fluorescence-Based Microplate Assay to Investigate the Interaction of Membrane Active Antimicrobial Peptides with Whole Gram-Positive Bacteria

Antibiotics ◽

10.3390/antibiotics9020092 ◽

2020 ◽

Vol 9 (2) ◽

pp. 92 ◽

Cited By ~ 2

Author(s):

Gerard Boix-Lemonche ◽

Maria Lekka ◽

Barbara Skerlavaj

Keyword(s):

Antimicrobial Peptides ◽

Staphylococcus Epidermidis ◽

Membrane Depolarization ◽

Membrane Permeabilization ◽

Microplate Assay ◽

Membrane Systems ◽

Gram Positive Bacteria ◽

Gramicidin D ◽

Membrane Effects ◽

Specific Membrane

Background: Membrane-active antimicrobial peptides (AMPs) are interesting candidates for the development of novel antimicrobials. Although their effects were extensively investigated in model membrane systems, interactions of AMPs with living microbial membranes are less known due to their complexity. The aim of the present study was to develop a rapid fluorescence-based microplate assay to analyze the membrane effects of AMPs in whole Staphylococcus aureus and Staphylococcus epidermidis. Methods: Bacteria were exposed to bactericidal and sub-inhibitory concentrations of two membrane-active AMPs in the presence of the potential-sensitive dye 3,3′-dipropylthiadicarbocyanine iodide (diSC3(5)) and the DNA staining dye propidium iodide (PI), to simultaneously monitor and possibly distinguish membrane depolarization and membrane permeabilization. Results: The ion channel-forming gramicidin D induced a rapid increase of diSC3(5), but not PI fluorescence, with slower kinetics at descending peptide concentrations, confirming killing due to membrane depolarization. The pore-forming melittin, at sub-MIC and bactericidal concentrations, caused, respectively, an increase of PI fluorescence in one or both dyes simultaneously, suggesting membrane permeabilization as a key event. Conclusions: This assay allowed the distinction between specific membrane effects, and it could be applied in the mode of action studies as well as in the screening of novel membrane-active AMPs.

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A New Type of Antimicrobial Phenolics Produced by Plant Peroxidase and Its Possible Role in the Chemical Defense Systems against Plant Pathogens

Zeitschrift für Naturforschung C ◽

10.1515/znc-1994-7-804 ◽

1994 ◽

Vol 49 (7-8) ◽

pp. 411-414 ◽

Cited By ~ 19

Author(s):

Akio Kobayashi ◽

Yutaka Koguchi ◽

Hiroshi Kanzaki ◽

Shin-ichiro Kajiyama ◽

Kazuyoshi Kawazu

Keyword(s):

Antimicrobial Activity ◽

Plant Pathogens ◽

Ethyl Acetate Extract ◽

Spectroscopic Techniques ◽

Antimicrobial Compounds ◽

Horse Radish Peroxidase ◽

Plant Peroxidase ◽

Defense Systems ◽

New Type ◽

Bacteria And Fungi

Syringaldehyde readily reacted in the horse-radish peroxidase (HRPOD) system. The ethyl acetate extract of the reaction mixture showed a marked antimicrobial activity against bacteria and fungi. After repeated column chromatography three potential antimicrobial compounds were obtained from the extract. The structural elucidation of active compounds was achieved by a combination of spectroscopic techniques and chemical modification

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From Antimicrobial to Anticancer Peptides: The Transformation of Peptides

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892814666190119165157 ◽

2019 ◽

Vol 14 (1) ◽

pp. 70-84 ◽

Cited By ~ 4

Author(s):

Yuan Qin ◽

Zuo D. Qin ◽

Jing Chen ◽

Che G. Cai ◽

Ling Li ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Tumor Cells ◽

Tumor Therapy ◽

Relevant Literature ◽

Point Of View ◽

Research Trend ◽

Gram Positive Bacteria ◽

Anticancer Peptides ◽

Search Data ◽

Tumor Drugs

Background: Antimicrobial peptides play an important role in the innate immune system. Possessing broad-spectrum antibacterial activity, antimicrobial peptides can quickly treat and kill various targets, including gram-negative bacteria, gram-positive bacteria, fungi, and tumor cells.Objective:An overview of the state of play with regard to the research trend of antimicrobial peptides in recent years and the situation of targeting tumor cells, and to make statistical analysis of the patents related to anticancer peptides published in recent years, is important both from toxicological and medical tumor therapy point of view.Methods:Based on the Science Citation Index Expanded version, the Derwent Innovation Index and Innography as data sources, the relevant literature and patents concerning antimicrobial peptides and anticancer peptides were analyzed through the Thomson Data Analyzer. Results of toxicologic and pharmacologic studies that brought to the development of patents for methods to novel tumor drugs were analyzed and sub-divided according to the specific synthesis of anticancer peptides.Results:The literature and patent search data show that the research and development of global antimicrobial peptides and anticancer peptides has been in an incremental mode. Growing patent evidence indicate that bioinformatics technology is a valuable strategy to modify, synthesize or recombine existing antimicrobial peptides to obtain tumor drugs with high activity, low toxicity and multiple targets.Conclusion:These findings may have important clinical implications for cancer treatment, especially in patients with conditions that are not currently treatable by other drugs, or that are resistant to existing cancer drugs.

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