scholarly journals Wide-Spectrum Biomimetic Antimicrobial Systems

Author(s):  
Heidi Weinkauf ◽  
Byron Brehm-Stecher

<p>Antimicrobial peptides (AMPs) are effective components of the host immune response and are widely distributed throughout nature. Recently, nontoxic antimicrobial polymers that mimic the structures of naturally occurring AMPs have been designed and are under development commercially as novel therapeutics. These compounds have several potential advantages over natural AMPs, including greater stability and reduced immunogenicity compared to natural peptides, relatively simple and scalable syntheses and the ability to tailor or &ldquo;fine tune&rdquo; their activities through combinatorial approaches. In previous work, we demonstrated the utility of certain generally regarded as safe (GRAS) flavorant and aroma compounds as enhancers of uptake and activity of clinically important antibiotics (Brehm-Stecher and Johnson, 2003). Here, we have extended this approach to include enhancement of biomimetic antimicrobial polymers. Three low molecular weight (&lt;1,000D), broad-spectrum arylamide polymers (PolyMedix, Inc., Radnor, PA) were examined for their antimicrobial activities against gram-negative bacteria, gram-positive bacteria, yeast and filamentous fungi, both alone and when co-administered with sesquiterpenoid enhancers. Assay formats included disk diffusion, automated turbidimetry, time course (kinetic) plating of antimicrobial-treated cell suspensions, outer membrane assays with 1 -N-phenylnaphthyl-amine (NPN) and transmission electron microscopy (TEM). Although results differed according to the polymer and test organism used, treatments containing sesquiterpenoids were marked either by increased ZOIs, decreased MICs or more rapid inactivation when compared with polymer-only treatments. Antimicrobial activity, expressed as decimal reduction times (D-value) showed that after 5 min the combination of sesquiterpenoid and polymer were significantly different from the controls (p&lt;0.05) with a D-value of 3.92 min when incubated with Escherichia coli ATCC 25922.&nbsp; Collectively, our results indicate that the combination of sesquiterpenoid enhancing agents with biomimetic antimicrobial polymers shows promise for the development of new, faster-acting and more broadly effective antimicrobial therapies.</p>

2019 ◽  
Vol 20 (11) ◽  
pp. 2747 ◽  
Author(s):  
Nor Fadhilah Kamaruzzaman ◽  
Li Peng Tan ◽  
Ruhil Hayati Hamdan ◽  
Siew Shean Choong ◽  
Weng Kin Wong ◽  
...  

Antimicrobial resistance is now considered a major global challenge; compromising medical advancements and our ability to treat infectious disease. Increased antimicrobial resistance has resulted in increased morbidity and mortality due to infectious diseases worldwide. The lack of discovery of novel compounds from natural products or new classes of antimicrobials, encouraged us to recycle discontinued antimicrobials that were previously removed from routine use due to their toxicity, e.g., colistin. Since the discovery of new classes of compounds is extremely expensive and has very little success, one strategy to overcome this issue could be the application of synthetic compounds that possess antimicrobial activities. Polymers with innate antimicrobial properties or that have the ability to be conjugated with other antimicrobial compounds create the possibility for replacement of antimicrobials either for the direct application as medicine or implanted on medical devices to control infection. Here, we provide the latest update on research related to antimicrobial polymers in the context of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. We summarise polymer subgroups: compounds containing natural peptides, halogens, phosphor and sulfo derivatives and phenol and benzoic derivatives, organometalic polymers, metal nanoparticles incorporated into polymeric carriers, dendrimers and polymer-based guanidine. We intend to enhance understanding in the field and promote further work on the development of polymer based antimicrobial compounds.


2021 ◽  
Vol 64 (2) ◽  
pp. 129-138
Author(s):  
Aruna Vigneshwari ◽  
Biljana D. Škrbić ◽  
László Kredics ◽  
Lubna Abbas ◽  
László Bakacsy ◽  
...  

Endophytes are a group of highly diverse microorganisms that reside within plant tissues without causing obvious symptoms on the host. In our study, Juniperus communis samples were collected from Hungary and used for the isolation of endophytic fungal strains. From 240 plant samples, 76 fungal isolates were recovered and subcultured for homogeneity. The isolates were identified using molecular taxonomical tools at the genus level and their biodiversity parameters were determined. The taxonomic diversity of the isolates was remarkably high, and the most abundant genera were Fusarium, Alternaria and Trichoderma. The secondary metabolites produced by the isolated endophytic fungi were extracted both from their mycelia and their ferment broth and their antimicrobial activities were tested against bacteria, yeasts, and filamentous fungi. In the antimicrobial tests, a total of 58 strains showed antimicrobial activity against at least one test organism. Altogether, 6.67% of the isolates have antibacterial effects with wide spectrum, and 10 strains showed remarkably high inhibitory percentage against yeast, while the extracts of 11 isolates proved to be active against filamentous fungi.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hessa H. Al-Rasheed ◽  
Kholood A. Dahlous ◽  
Essam N. Sholkamy ◽  
Sameh M. Osman ◽  
Omar H. Abd-Elkader ◽  
...  

Herein, we described the modification of chitosan with cyanuric chloride as a mediator for preparation of chitosan-s-triazinyl-bis(2-aminomethylpyridine) and chitosan-s-triazinyl-bis(8-oxyquinoline) derivatives to be used as reagents for preparation of silver nanoparticles under ecofriendly conditions. These two reagents are convenient and effective for reduction of silver ions to silver nanoparticles with particle size less than 10 nm that might be suitable for industrial and medicinal applications. The formation and particle size of AgNPs are characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray analysis (EDX). The antimicrobial activity of the two modified chitosan-s-triazine-AgNPs was evaluated against activities against Gram-positive bacteria (M. luteus ATCC 10240 and MRSA ATCC 43300), Gram-negative bacteria (E. coli ATCC 25922 and P. aeruginosa ATCC 75853), and C. albicans. The results showed that chitosan-s-triazinyl-bis(2-aminomethylpyridine) AgNPs showed high antimicrobial activities against all the tested microorganisms, while their analogous chitosan-s-triazinyl-bis(8-oxyquinoline) AgNPs showed moderate activities.


Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 163 ◽  
Author(s):  
Yuzuru Kubohara ◽  
Yoshiko Shiratsuchi ◽  
Hirotaka Ishigaki ◽  
Katsunori Takahashi ◽  
Yoshiteru Oshima ◽  
...  

At the end of its life cycle, the cellular slime mold Dictyostelium discoideum forms a fruiting body consisting of spores and a multicellular stalk. Originally, the chlorinated alkylphenone differentiation-inducing factors (DIFs) -1 and -3 were isolated as stalk cell inducers in D. discoideum. Later, DIFs and their derivatives were shown to possess several biologic activities including antitumor and anti-Trypanosoma properties. In this study, we examined the antibacterial activities of approximately 30 DIF derivatives by using several bacterial species. Several of the DIF derivatives strongly suppressed the growth of the Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis and Enterococcus faecium, at minimum inhibitory concentrations (MICs) in the sub-micromolar to low-micromolar range. In contrast, none of the DIF derivatives evaluated had any noteworthy effect on the growth of the Gram-negative bacterium Escherichia coli (MIC, >100 µM). Most importantly, several of the DIF derivatives strongly inhibited the growth of methicillin-resistant S. aureus and vancomycin-resistant E. faecalis and E. faecium. Transmission electron microscopy revealed that treatment with DIF derivatives led to the formation of distinct multilayered structures consisting of cell wall or plasma membrane in S. aureus. The present results suggest that DIF derivatives are good lead compounds for developing novel antimicrobials.


2021 ◽  
Vol 22 (7) ◽  
pp. 3343
Author(s):  
Hideo Yonezawa ◽  
Mizuho Motegi ◽  
Atsushi Oishi ◽  
Fuhito Hojo ◽  
Seiya Higashi ◽  
...  

Lantibiotics are a type of bacteriocin produced by Gram-positive bacteria and have a wide spectrum of Gram-positive antimicrobial activity. In this study, we determined that Mutacin I/III and Smb (a dipeptide lantibiotic), which are mainly produced by the widespread cariogenic bacterium Streptococcus mutans, have strong antimicrobial activities against many of the Gram-positive bacteria which constitute the intestinal microbiota. These lantibiotics also demonstrate resistance to acid and temperature. Based on these features, we predicted that lantibiotics may be able to persist into the intestinal tract maintaining a strong antimicrobial activity, affecting the intestinal microbiota. Saliva and fecal samples from 69 subjects were collected to test this hypothesis and the presence of lantibiotics and the composition of the intestinal microbiota were examined. We demonstrate that subjects possessing lantibiotic-producing bacteria in their oral cavity exhibited a tendency of decreased species richness and have significantly reduced abundance of the phylum Firmicutes in their intestinal microbiota. Similar results were obtained in the fecal microbiota of mice fed with S. mutans culture supernatant containing the lantibiotic bacteriocin Mutacin I. These results showed that lantibiotic bacteriocins produced in the oral cavity perturb the intestinal microbiota and suggest that oral bacteria may be one of the causative factors of intestinal microbiota dysbiosis.


1997 ◽  
Vol 161 ◽  
pp. 491-504 ◽  
Author(s):  
Frances Westall

AbstractThe oldest cell-like structures on Earth are preserved in silicified lagoonal, shallow sea or hydrothermal sediments, such as some Archean formations in Western Australia and South Africa. Previous studies concentrated on the search for organic fossils in Archean rocks. Observations of silicified bacteria (as silica minerals) are scarce for both the Precambrian and the Phanerozoic, but reports of mineral bacteria finds, in general, are increasing. The problems associated with the identification of authentic fossil bacteria and, if possible, closer identification of bacteria type can, in part, be overcome by experimental fossilisation studies. These have shown that not all bacteria fossilise in the same way and, indeed, some seem to be very resistent to fossilisation. This paper deals with a transmission electron microscope investigation of the silicification of four species of bacteria commonly found in the environment. The Gram positiveBacillus laterosporusand its spore produced a robust, durable crust upon silicification, whereas the Gram negativePseudomonas fluorescens, Ps. vesicularis, andPs. acidovoranspresented delicately preserved walls. The greater amount of peptidoglycan, containing abundant metal cation binding sites, in the cell wall of the Gram positive bacterium, probably accounts for the difference in the mode of fossilisation. The Gram positive bacteria are, therefore, probably most likely to be preserved in the terrestrial and extraterrestrial rock record.


Author(s):  
P. Maupin-Szamier ◽  
T. D. Pollard

We have studied the destruction of rabbit muscle actin filaments by osmium tetroxide (OSO4) to develop methods which will preserve the structure of actin filaments during preparation for transmission electron microscopy.Negatively stained F-actin, which appears as smooth, gently curved filaments in control samples (Fig. 1a), acquire an angular, distorted profile and break into progressively shorter pieces after exposure to OSO4 (Fig. 1b,c). We followed the time course of the reaction with viscometry since it is a simple, quantitative method to assess filament integrity. The difference in rates of decay in viscosity of polymerized actin solutions after the addition of four concentrations of OSO4 is illustrated in Fig. 2. Viscometry indicated that the rate of actin filament destruction is also dependent upon temperature, buffer type, buffer concentration, and pH, and requires the continued presence of OSO4. The conditions most favorable to filament preservation are fixation in a low concentration of OSO4 for a short time at 0°C in 100mM sodium phosphate buffer, pH 6.0.


2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Junpeng Li ◽  
Shuping Hu ◽  
Wei Jian ◽  
Chengjian Xie ◽  
Xingyong Yang

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.


Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1343
Author(s):  
Caroline Tyavambiza ◽  
Abdulrahman Mohammed Elbagory ◽  
Abram Madimabe Madiehe ◽  
Mervin Meyer ◽  
Samantha Meyer

Cotyledon orbiculata, commonly known as pig’s ear, is an important medicinal plant of South Africa. It is used in traditional medicine to treat many ailments, including skin eruptions, abscesses, inflammation, boils and acne. Many plants have been used to synthesize metallic nanoparticles, particularly silver nanoparticles (AgNPs). However, the synthesis of AgNPs from C. orbiculata has never been reported before. The aim of this study was to synthesize AgNPs using C. orbiculata and evaluate their antimicrobial and immunomodulatory properties. AgNPs were synthesized and characterized using Ultraviolet-Visible Spectroscopy (UV-Vis), Dynamic Light Scattering (DLS) and High-Resolution Transmission Electron Microscopy (HR-TEM). The antimicrobial activities of the nanoparticles against skin pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Methicillin Resistance Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans) as well as their effects on cytokine production in macrophages (differentiated from THP-1 cells) were evaluated. The AgNPs from C. orbiculata exhibited antimicrobial activity, with the highest activity observed against P. aeruginosa (5 µg/mL). The AgNPs also showed anti-inflammatory activity by inhibiting the secretion of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1 beta) in lipopolysaccharide-treated macrophages. This concludes that the AgNPs produced from C. orbiculata possess antimicrobial and anti-inflammation properties.


2000 ◽  
Vol 44 (4) ◽  
pp. 848-852 ◽  
Author(s):  
C. M. Kunin ◽  
W. Y. Ellis

ABSTRACT Mefloquine was found to have bactericidal activity against methicillin- and fluoroquinolone-susceptible and -resistant strains ofStaphylococcus aureus and Staphylococcus epidermidis and gentamicin- and vancomycin-resistant strains ofEnterococcus faecalis and Enterococcus faecium. The MICs were 16 μg/ml, and the minimal bactericidal concentrations (MBCs) were 16 to 32 μg/ml. These concentrations cannot be achieved in serum. Mefloquine was active at a more achievable concentration against penicillin-susceptible and -resistant Streptococcus pneumoniae, with MICs of 0.2 to 1.5 μg/ml. Mefloquine was not active against gram-negative bacteria and yeasts. In an attempt to find more active derivatives, 400 mefloquine-related compounds were selected from the chemical inventory of The Walter Reed Army Institute of Research. We identified a series of compounds containing a piperidine methanol group attached to pyridine, quinoline, and benzylquinoline ring systems. These had activities similar to that of mefloquine against S. pneumoniae but were far more active against other gram-positive bacteria (MICs for staphylococci, 0.8 to 6.3 μg/ml). They had activities similar to that of amphotericin B againstCandida spp. and Cryptococcus neoformans. Combinations of the compounds with gentamicin and vancomycin were additive against staphylococci and pneumococci. The MIC and MBC of gentamicin were decreased by four- to eightfold when this drug was combined with limiting dilutions of the compounds. There was no antagonism with other antimicrobial drugs. The compounds were rapidly bactericidal. They appear to act by disrupting cell membranes. Combinations of the compounds with aminoglycoside antibiotics may have potential for therapeutic use.


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