A Short Peptide Derived from the ZorO Toxin Functions as an Effective Antimicrobial

Antimicrobial peptides are potential molecules for the development of novel antibiotic agents. The ZorO toxin of a type I toxin–antitoxin system in Escherichia coli O157:H7 is composed of 29 amino acids and its endogenous expression inhibits E. coli growth. However, little is known about its inhibitory mechanism. In this study, we demonstrate that the ZorO localized in the inner membrane affects the plasma membrane integrity and potential when expressed in E. coli cells, which triggers the production of cytotoxic hydroxyl radicals. We further show that five internal amino acids (Ala–Leu–Leu–Arg–Leu; ALLRL) of ZorO are necessary for its toxicity. This result prompted us to address the potential of the synthetic ALLRL peptide as an antimicrobial. Exogenously-added ALLRL peptide to Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and a fungus, Candida albicans, trigger cell membrane damage and exhibit growth defect, while having no effect on Gram-negative bacterium, E. coli. The ALLRL peptide retains its activity under the physiological salt concentrations, which is in contrast to natural antimicrobial peptides. Importantly, this peptide has no toxicity against mammalian cells. Taken together, an effective and short peptide, ALLRL, would be an attractive antimicrobial to Gram-positive bacteria and C. albicans.

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Identification of Ly2 members as antimicrobial peptides from zebrafish Danio rerio

Bioscience Reports ◽

10.1042/bsr20160265 ◽

2017 ◽

Vol 37 (1) ◽

Cited By ~ 6

Author(s):

Xuemin Liu ◽

Xuwen Cao ◽

Su Wang ◽

Guangdong Ji ◽

Shicui Zhang ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Recombinant Proteins ◽

Mammalian Cells ◽

Multidrug Resistant ◽

Scatchard Analysis ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Gram Positive Bacteria

The emergence of multidrug-resistant (MDR) microbes caused by overuse of antibiotics leads to urgent demands for novel antibiotics exploration. Our recent data showed that Ly2.1–3 (a novel lymphocyte antigen 6 (Ly6) gene cluster) were proteins with cationic nature and rich in cysteine content, that are characteristic of antimicrobial peptides (AMPs) and their expression were all significantly up-regulated after challenge with lipopolysaccharide (LPS). These strongly suggested that Ly2.1–3 are potential AMPs, but firm evidence are lacking. Here, we clearly showed that the recombinant proteins of Ly2.1–3 were capable of killing Gram-negative bacteria Aeromonas hydrophila and Escherichia coli, while they had little bactericidal activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis. We also showed that recombinant proteins Ly2.1–3 (rLy2.1–3) were able to bind to the Gram-negative bacteria A. hydrophila, E. coli and the microbial signature molecule LPS, but not to the Gram-positive bacteria S. aureus and B. subtilis as well as the microbial signature molecule LTA. Moreover, the Scatchard analysis revealed that rLy2.1–3 could specifically bind to LPS. Finally, we found that Ly2.1–3 were not cytotoxic to mammalian cells. All these together indicate that Ly2.1–3 can function as AMPs.

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Synthesis, Characterization, and Antimicrobial Properties of Peptides Mimicking Copolymers of Maleic Anhydride and 4-Methyl-1-pentene

International Journal of Molecular Sciences ◽

10.3390/ijms19092617 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2617 ◽

Cited By ~ 4

Author(s):

Marian Szkudlarek ◽

Elisabeth Heine ◽

Helmut Keul ◽

Uwe Beginn ◽

Martin Möller

Keyword(s):

Maleic Anhydride ◽

Mammalian Cells ◽

Antimicrobial Properties ◽

Amphiphilic Copolymers ◽

Gram Positive ◽

One Pot ◽

E Coli ◽

Gram Positive Bacteria ◽

Alternating Copolymer ◽

The Difference

Synthetic amphiphilic copolymers with strong antimicrobial properties mimicking natural antimicrobial peptides were obtained via synthesis of an alternating copolymer of maleic anhydride and 4-methyl-1-pentene. The obtained copolymer was modified by grafting with 3-(dimethylamino)-1-propylamine (DMAPA) and imidized in a one-pot synthesis. The obtained copolymer was modified further to yield polycationic copolymers by means of quaternization with methyl iodide and dodecyl iodide, as well as by being sequentially quaternized with both of them. The antimicrobial properties of obtained copolymers were tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus. Both tested quaternized copolymers were more active against the Gram-negative E. coli than against the Gram-positive S. aureus. The copolymer modified with both iodides was best when tested against E. coli and, comparing all three copolymers, also exhibited the best effect against S. aureus. Moreover, it shows (limited) selectivity to differentiate between mammalian cells and bacterial cell walls. Comparing the minimum inhibitory concentration (MIC) of Nisin against the Gram-positive bacteria on the molar basis instead on the weight basis, the difference between the effect of Nisin and the copolymer is significantly lower.

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A novel bis(pyrazolyl)methane compound as a potential agent against Gram-positive bacteria

Scientific Reports ◽

10.1038/s41598-021-95609-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Pedro Seguí ◽

John J. Aguilera-Correa ◽

Elena Domínguez-Jurado ◽

Christian M. Sánchez-López ◽

Ramón Pérez-Tanoira ◽

...

Keyword(s):

Antibacterial Activity ◽

Inhibitory Effect ◽

Eukaryotic Cell ◽

Liver Carcinoma ◽

Gram Positive ◽

Minimal Inhibitory Concentrations ◽

E Coli ◽

Gram Positive Bacteria ◽

Therapeutic Compounds ◽

Toxic Concentrations

AbstractThis study was designed to propose alternative therapeutic compounds to fight against bacterial pathogens. Thus, a library of nitrogen-based compounds bis(triazolyl)methane (1T–7T) and bis(pyrazolyl)methane (1P–11P) was synthesised following previously reported methodologies and their antibacterial activity was tested using the collection strains of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Moreover, the novel compound 2P was fully characterized by IR, UV–Vis and NMR spectroscopy. To evaluate antibacterial activity, minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) assays were carried out at different concentrations (2–2000 µg/mL). The MTT assay and Resazurin viability assays were performed in both human liver carcinoma HepG2 and human colorectal adenocarcinoma Caco-2 cell lines at 48 h. Of all the synthesised compounds, 2P had an inhibitory effect on Gram-positive strains, especially against S. aureus. The MIC and MBC of 2P were 62.5 and 2000 µg/mL against S. aureus, and 250 and 2000 µg/mL against E. faecalis, respectively. However, these values were > 2000 µg/mL against E. coli and P. aeruginosa. In addition, the MBICs and MBECs of 2P against S. aureus were 125 and > 2000 µg/mL, respectively, whereas these values were > 2000 µg/mL against E. faecalis, E. coli, and P. aeruginosa. On the other hand, concentrations up to 250 µg/mL of 2P were non-toxic doses for eukaryotic cell cultures. Thus, according to the obtained results, the 2P nitrogen-based compound showed a promising anti-Gram-positive effect (especially against S. aureus) both on planktonic state and biofilm, at non-toxic concentrations.

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Preparation of bioactive and antibacterial PMMA-based bone cement by modification with quaternary ammonium and alkoxysilane

Journal of Biomaterials Applications ◽

10.1177/08853282211004413 ◽

2021 ◽

pp. 088532822110044

Author(s):

Haiyang Wang ◽

Toshinari Maeda ◽

Toshiki Miyazaki

Keyword(s):

Antibacterial Activity ◽

Methyl Methacrylate ◽

Bone Cement ◽

Setting Time ◽

Antibacterial Properties ◽

The Body ◽

Apatite Formation ◽

Gram Positive ◽

E Coli ◽

Gram Positive Bacteria

Bone cement based on poly(methyl methacrylate) (PMMA) powder and methyl methacrylate (MMA) liquid is a very popular biomaterial used for the fixation of artificial joints. However, there is a risk of this cement loosening from bone because of a lack of bone-bonding bioactivity. Apatite formation in the body environment is a prerequisite for cement bioactivity. Additionally, suppression of infection during implantation is required for bone cements to be successfully introduced into the human body. In this study, we modified PMMA cement with γ-methacryloxypropyltrimetoxysilane and calcium acetate to introduce bioactive properties and 2-( tert-butylamino)ethyl methacrylate (TBAEMA) to provide antibacterial properties. The long-term antibacterial activity is attributed to the copolymerization of TBAEMA and MMA. As the TBAEMA content increased, the setting time increased and the compressive strength decreased. After soaking in simulated body fluid, an apatite layer was detected within 7 days, irrespective of the TBAEMA content. The cement showed better antibacterial activity against Gram-negative E. Coli than Gram-positive bacteria; however, of the Gram-positive bacteria investigated, B. subtilis was more susceptible than S. aureus.

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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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Construction of Leaderless-Bacteriocin-Producing Bacteriophage Targeting E. coli and Neighboring Gram-Positive Pathogens

Microbiology Spectrum ◽

10.1128/spectrum.00141-21 ◽

2021 ◽

Author(s):

Yoshimitsu Masuda ◽

Shun Kawabata ◽

Tatsuya Uedoi ◽

Ken-ichi Honjoh ◽

Takahisa Miyamoto

Keyword(s):

Antimicrobial Agents ◽

Host Strain ◽

Phage Resistance ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Gram Positive Bacteria ◽

T7 Phage

We demonstrated that we could combine LLB and phage to construct promising novel antimicrobial agents, LLB-phage. The first LLB-phage, lnqQ -T7 phage, can control the growth of both the Gram-negative host strain and neighboring Gram-positive bacteria while preventing the emergence of phage resistance in the host strain.

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Type I and Type II mechanisms of antimicrobial photodynamic therapy: An in vitro study on gram-negative and gram-positive bacteria

Lasers in Surgery and Medicine ◽

10.1002/lsm.22045 ◽

2012 ◽

Vol 44 (6) ◽

pp. 490-499 ◽

Cited By ~ 168

Author(s):

Liyi Huang ◽

Yi Xuan ◽

Yuichiro Koide ◽

Timur Zhiyentayev ◽

Masamitsu Tanaka ◽

...

Keyword(s):

Photodynamic Therapy ◽

In Vitro Study ◽

Vitro Study ◽

Type I ◽

Antimicrobial Photodynamic Therapy ◽

Type Ii ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

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Assimilation of Amino Acids by Gram-Positive Bacteria and Some Actions of Antibiotics Thereon

Advances in Protein Chemistry ◽

10.1016/s0065-3233(08)60094-7 ◽

1953 ◽

pp. 285-391 ◽

Cited By ~ 54

Author(s):

Ernest F. Gale

Keyword(s):

Amino Acids ◽

Gram Positive ◽

Gram Positive Bacteria

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Water-dispersible glycosylated poly(2,5′-thienylene)porphyrin-based nanoparticles for antibacterial photodynamic therapy

Photochemical & Photobiological Sciences ◽

10.1039/c8pp00470f ◽

2019 ◽

Vol 18 (5) ◽

pp. 1147-1155 ◽

Cited By ~ 5

Author(s):

Rehan Khan ◽

Melis Özkan ◽

Aisan Khaligh ◽

Dönüs Tuncel

Keyword(s):

Antibacterial Activity ◽

Photodynamic Therapy ◽

Singlet Oxygen ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Water Dispersible ◽

Gram Positive Bacteria ◽

High Yields

Water-dispersible glycosylated poly(2,5′-thienylene)porphyrin-based nanoparticles have the ability to generate singlet oxygen in high yields and exhibit light-triggered antibacterial activity against Gram negative bacteria, E. coli as well as Gram positive bacteria, B. subtilis.

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