Increase In Antimicrobial Activity Research Articles

Conjugation of Polycationic Peptides Extends the Efficacy Spectrum of β-Lactam Antibiotics.

Antibiotic-resistant enterococci represent a significant global health challenge. Unfortunately, most β-lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of β-lactam antibiotics. Remarkably, the β-lactam-peptide conjugates gained an up to 1000-fold increase in antimicrobial activity against vancomycin-susceptible and vancomycin-resistant enterococci. Even against β-lactam-resistant Gram-negative strains, the conjugates are found to be effective despite their size exceeding the exclusion volume of porins. The extraordinary gain of activity can be explained by an altered mode of killing. Of note, the conjugates showed a concentration-dependent activity in contrast to the parent β-lactam antibiotics that exhibited a time-dependent mode of action. In comparison to the parent β-lactams, the conjugates showed altered affinities to the penicillin-binding proteins. Furthermore, it is found that peptide conjugation also resulted in a different elimination route of the compounds when administered to rodents. In mice systemically infected with vancomycin-resistant enterococci, treatment with a β-lactam-peptide conjugate reduced bacterial burden in the liver compared to its originator. Therefore, peptide modification of β-lactam antibiotics represents a promising platform strategy to broaden their efficacy spectrum, particularly against enterococci.

Chemical characterization and antibacterial activities of Brazilian propolis extracts from Apis mellifera bees and stingless bees (Meliponini).

The aim of this study was to evaluate the physicochemical composition and antibacterial activity of Brazilian propolis extracts from different types, concentrations, and extraction solvents and from different regions in Brazil. A total of 21 samples were analyzed, comprising 14 samples from Apis mellifera (12 green, 1 brown, and 1 red) and 7 samples from stingless bees (3 mandaçaia, 2 jataí, 1 hebora, and 1 tubuna). The analyses performed were dry extract, total phenolic content (TPC) and antioxidant activity (DPPH and ABTS). The antibacterial activity was performed by Determination of Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC). The results showed that very low levels of phenolic compounds and antioxidant activity decreased the antimicrobial activity of the propolis extracts from tubuna and jataí. However, there was no correlation between the increase in propolis concentration in the extract, and the increase in antimicrobial activity. The highest TPC and antioxidant activity was obtained for green propolis extract made with 70% raw propolis that presented similar antibacterial activity to the samples formulated with 30% or less raw propolis. The aqueous propolis extract showed lower antimicrobial activity compared to the alcoholic extracts, indicating that ethanol is a better solvent for extracting the active compounds from propolis. It was observed that the MIC (0.06 to 0.2 mg/mL) and MBC (0.2 to 0.5 mg/mL) values for Gram-negative bacteria were higher compared to Gram-positive bacteria (MIC 0.001-0.2 mg/mL, and the MBC 0.02-0.5 mg/mL). The propolis extracts that exhibited the highest antimicrobial activities were from stingless bees hebora from the Distrito Federal (DF) and mandaçaia from Santa Catarina, showing comparable efficacy to samples 5, 6, and 7, which were the green propolis from the DF. Hence, these products can be considered an excellent source of bioactive compounds with the potential for utilization in both the pharmaceutical and food industries.

Sensing and Microbiological Activity of a New Blue Fluorescence Polyamidoamine Dendrimer Modified with 1,8-Naphthalimide Units.

A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4-N,N-dimethylaninoethyloxy-1,8-naphthalimide units was synthesized. Its basic photophysical characteristics were investigated in organic solvents of different polarity. It was found that in these solvents, the dendrimer is colorless and emitted blue fluorescence with different intensities depending on their polarity. The effect of the pH of the medium on the fluorescence intensity was investigated and it was found that in the acidic medium, the fluorescence is intense and is quenched in the alkaline medium. The ability of the dendrimer to detect metal ions (Pb2+, Zn2+, Mg2+, Sn2+, Ba2+, Ni2+, Sn2+, Mn2+, Co2+, Fe3+, and Al3+) was also investigated, and it was found that in the presence of Fe3+, the fluorescent intensity was amplified more than 66 times. The antimicrobial activity of the new compound has been tested in vitro against Gram-positive B. cereus and Gram-negative P. aeruginosa. The tests were performed in the dark and after irradiation with visible light. The antimicrobial activity of the compound enhanced after light irradiation and B. cereus was found slightly more sensitive than P. aeruginosa. The increase in antimicrobial activity after light irradiation is due to the generation of singlet oxygen particles, which attack bacterial cell membranes.

The Potential of Pediococcus acidilactici Cell-Free Supernatant as a Preservative in Food Packaging Materials.

This study delves into the production and antimicrobial characteristics of cell-free supernatants from Pediococcus acidilactici (CFSs-Pa). Antimicrobial activity was initially observed in CFS-Pa harvested after 12 h of incubation and increased up to the late stationary phase at 48 h. The increase in antimicrobial activity did not align with total protein content, pointing to other factors linked to the accumulation of organic acids, particularly lactic acid. The SDS-PAGE analysis also indicated that the expected proteinaceous compound (pediocin) was not observed in CFS-Pa. Further investigations suggested that the antimicrobial properties of CFS-Pa were exclusively due to organic acids. The MIC values confirmed potent antimicrobial activity, particularly at a 10% dilution of CFS-Pa in MRS broth. The time-kill assays demonstrated bactericidal activity against EHEC, Listeria monocytogenes, and Staphylococcus aureus by 12 h, 18 h, and 24 h using a 10% dilution of CFS-Pa. Additionally, CFS-Pa exhibited dose-dependent antioxidant activity, requiring a 70% (v/v) concentration to inhibit DPPH scavenging activity by 50%. All the experimental results suggested potential applications of CFS-Pa in food preservation. An attempt to incorporate CFS-Pa into bacterial cellulose (BC) for edible food packaging demonstrated promising antimicrobial results, particularly against L. monocytogenes and S. aureus, with room for optimization.

Nanotherapeutic delivery of antibiotic cocktail enhances intra-macrophage killing of Mycobacterium marinum

Mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in cold-blooded animals and is an opportunistic pathogen in humans. M. marinum is the closest genetic relative of the Mycobacterium tuberculosis complex and is a reliable surrogate for drug susceptibility testing. We synthesized and evaluated two nanoparticle (NP) formulations for compatibility with rifampicin, isoniazid, pyrazinamide, and ethambutol (PIRE), the front-line antimycobacterial drugs used in combination against active tuberculosis infections. Improved in vitro antimicrobial activity was observed with encapsulated rifampicin alone or in a cocktail of drugs formulated through co-encapsulation in amphiphilic polyanhydride NPs. Broth antimicrobial testing revealed that the encapsulation of PIRE in NP resulted in a significant increase in antimicrobial activity, with the benefit over soluble formulations at biologically relevant concentrations ranging from >10 to >3,000 fold. M. marinum-infected human macrophages treated with NP-PIRE were cleared of viable bacteria in 48 h following a single treatment, representing a >4 log reduction in colony-forming units and a >2,000-fold increase in antimicrobial activity. The amphiphilic polyanhydride nanoparticles demonstrated the ability to co-encapsulate PIRE antibiotics and enhance their antimicrobial activity against M. marinum in infected macrophages in culture and in vitro. These data suggest that polyanhydride nanoparticles are a promising nanotherapeutic for combatting Mycobacterium infections through improved intracellular targeting of encapsulated antibiotics.

ANTIMICROBIAL ACTIVITY OF BUTANOL COMPLEXES AND ISOLATED SECONDARY METABOLITES OF SOME SPECIES OF GENUS SILENE OF THE FAMILY CARYOPHYLLACEAE

Extracts of 9 species of the Caryophyllaceae family were screened for antimicrobial activity on the example of 17 types of strains of microorganisms. The inhibitory activity of 7 butanol extracts has been shown against a number of pathogenic strains belonging to the species Mycobacterium smegmatis, Phroteus mirabilis, Serratia marcescens, Staphylococcus aureus, Streptococcus faecalis. The extracts studied were most effective on the bacteria Bacillus cereus and Bacillus subtilis. It was found that all the studied plant species of the genera Lychnis and Silene contain ecdysteroids and flavonoids. The isolated individual compounds contained in all the studied species showed antimicrobial action on strains of a number of bacteria: the ecdysteroid 20-hydroxyecdysone suppressed the growth of the strain of R. mirabilis, while the flavonoid shaftoside inhibited strains of bacteria S. aureus, B. cereus, B. subtilis, R. mirabilis, M. smegmatis. Gram-negative bacteria Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Pseudomonas aeruginosa are not susceptible to the antimicrobial action of extracts under experimental conditions.
 Determination of antimicrobial activity was carried out by methods – diffusion and joint incubation of plant extracts and cells of test strains of microorganisms in a liquid nutrient medium LB at the ratio sample : medium 1 : 2 and 1 : 1. Increase in the concentration of secondary metabolites of ecdysteroids and flavonoids in experiments with butanol complexes of substances with a sample ratio the 1 : 1 environment led to an increase in antimicrobial activity up to the complete inhibition of Gram-positive bacteria B. subtilis and B. cereus by extracts of plant species Silene graefferi, S. colpophylla, S. sendtneri, S. linicola, S. jenisseensis S. viridiflora (seeds) and individual shaftoside.

Biomimetic Hydroxyapatite Crystals Growth on Phosphorylated Chitosan Films by In Vitro Mineralization Used as Dental Substitute Materials.

Chitosan (CS) films exhibit great potential as a substrate for the in vitro mineralization process. In this study, to mimic the formation of nanohydroxyapatite (HAP) as natural tissue, CS films coated with a porous calcium phosphate were investigated using scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), Fourier transforms infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). Calcium phosphate coating deposited on phosphorylated derivatives of CS was obtained by a process based on phosphorylation, Ca(OH)2 treatment and artificial saliva solution (ASS) immersion. The phosphorylated CS films (PCS) were obtained by partial hydrolysis of the PO4 functionalities. It was demonstrated that this precursor phase could induce the growth and the nucleation of the porous calcium phosphate coating when immersed in ASS. Moreover, oriented crystals and qualitative control of calcium phosphate phases on CS matrices are obtained in a biomimetic mode. Furthermore, in vitro antimicrobial activity of PCS was evaluated against three species of oral bacteria and fungi. It revealed an increase in antimicrobial activity with minimum inhibition concentration (MIC) values of 0.10% (Candida albicans), 0.05% (Staphylococcus aureus) and 0.025% (Escherichia coli) which proves their possible use as dental substitute materials.

Interaction of bifunctional peptide-carbazole complexes with DNA and antimicrobial activity

Two peptide-carbazole conjugates, CTAT and CNLS, were designed and synthesized using carbazole Schiff base to modify the cell membrane penetrating peptide TAT (47–57) and the nuclear localization peptide NLS at the N terminus. The interaction with ctDNA was investigated by multispectral and agarose gel electrophoresis. And the effects of CNLS and CTAT on the G-quadruplex structure were explored by circular dichroism titration experiments. The results show that both CTAT and CNLS interact with ctDNA in a minor groove binding manner. Both conjugates bind more tightly to DNA than the individual substances CIBA, TAT and NLS. In addition, CTAT and CNLS are capable of unfolding parallel G-quadruplex structures and are potential G-quadruplex unfolding agents. Finally, broth microdilution was performed to test the antimicrobial activity of the peptides. The results showed that CTAT and CNLS had a 4-fold increase in antimicrobial activity compared with the parent peptides TAT and NLS. They could exert antimicrobial activity by disrupting the integrity of cell membrane bilayer and binding to DNA, and could be used as novel antimicrobial peptides for the development of novel antimicrobial antibiotics.

Silver Nanoparticles Enhance the Antibacterial Effect of Antibiotic-Loaded Bone Cement.

Purpose The goal of this study was to determine the antibacterial activity of bone cement in polymethyl methacrylate (PMMA) structures with varying amounts of silver nanoparticles (AgNPs) included. Additionally, we aimed to evaluate whether AgNPs affect the biomechanical properties of PMMA cement in our study. Materials and methods Between April 2020 and June 2020, we conducted a series of experiments to demonstrate the antibacterial characteristics by adding silver nanoparticles to PMMA bone cement.PMMA bone cement (Cemex, Tecres Company, Verona, Italy) was used as the base material. Seven different samples were prepared in order to evaluate the amount and presence of AgNPs. Cement samples containing AgNPs and teicoplanin at different concentrations and empty cement (control, without teicoplanin and AgNPs) were placed on Petri plates. The agar diffusion method was used to determine the antibacterial effect (Kirby-Bauer). Results Kirby-Bauer assays demonstrated that AgNPs added to bone cement increased the antimicrobial activity compared to antibiotic-free or only teicoplanin-loaded cement. It was observed that increasing the AgNPs ratio further increased the antimicrobial activity. Conclusion AgNPs in various combinations enhance antimicrobial activity synergistically while maintaining the mechanical strength of bone cement. Increasing the amount of AgNPs results in a significant increase in antimicrobial activity.

MODIFICATION NANO-SIZE OF ZINC OXIDE (ZnO-NS) WITH POLYETHYLENE GLYCOL AND APPLICATION AS ANTIMICROBIAL

Sol-gel is a simple method used to synthesize nano-size ZnO (ZnO-NS) in many applications. It acts as an antimicrobial agent for Escherichia coli and Aspergillus niger infections. The nano-size and patterned nanorods structure of ZnO enhances anti-microbial properties. This study used Polyethylene Glycol (PEG-6000) polymer compounds with variations in their 3, 5, and 10% compositions as templates for the formation of the nanorods. The morphology of the ZnO-NS produced determined the increase in anti-microbial activity. Furthermore, those generated from 5% PEG composition (ZnO/PEG-5) have the smallest size with the greatest anti-microbial activity on inhibition zones against E. coli and A. niger, each of 8.5-10.5 mm. There are morphological differences in each variable in the homogeneity distribution level of the spherical and rod dimension patterns of ZnO-NS. This is based on characterization with UV-VIS-DRS and Fourier-Transform infrared (FT-IR) for the analysis of Zn-O interactions at wave number 500-550 cm-1. Field Emission Scanning Electron Microscopy-Dispersive Scanning Electron Microscope (FE-SEM) and Energy dispersive X-ray spectroscopy (EDX) was used for dimensional pattern analysis, while X-ray diffraction (XRD) was applied for hexagonal wurtzite ZnO structures following the ICSD-65122 standard.

Synthesis of Sulfated Chitosan Through Sulfation Reaction of Chitosan with Chlorosulfonic Acid in N, N-Dimethylformamide, and Antibacterial Activity Test

Sulfated chitosan has been successfully synthesized through sulfation reaction between chitosan and chlorosulfonic acid using catalyst and N, N-Dimethylformamide (DMF) solvent. The first step was sulfation of chitosan with 4; 4.5; 5 mL of HClSO3. The formation of sulfated chitosan was supported by an increased solubility in water and the appearance of peaks at 1111 cm-1, which indicated the C-O-S group. Sulfated chitosan that has been produced, has a degree of sulfation of 5.6041%; 6.0045%; 6.8051%. Sulfated chitosan shows moderate antibacterial activity and a wide spectrum of antibacterial properties against Escherichia coli and Staphylococcus aureus bacterias. The increase in the degree of sulfation was proportional to the increase in antimicrobial activity of both bacteria. The highest antibacterial activity based on inhibitory zone diameter was 10 mm for sulfated chitosan that has been produced from 1 g of chitosan with 5 mL of HClSO3 with a degree of sulfation was 6.8051%.

New Zinc-Based Active Chitosan Films: Physicochemical Characterization, Antioxidant, and Antimicrobial Properties.

The improvement of the antioxidant and antimicrobial activities of chitosan (CS) films can be realized by incorporating transition metal complexes as active components. In this context, bioactive films were prepared by embedding a newly synthesized acylpyrazolonate Zn(II) complex, [Zn(QPhtBu)2(MeOH)2], into the eco-friendly biopolymer CS matrix. Homogeneous, amorphous, flexible, and transparent CS@Znn films were obtained through the solvent casting method in dilute acidic solution, using different weight ratios of the Zn(II) complex to CS and characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR), Raman, and scanning electron microscopy (SEM) techniques. The X-ray single-crystal analysis of [Zn(QPhtBu)2(MeOH)2] and the evaluation of its intermolecular interactions with a protonated glucosamine fragment through hydrogen bond propensity (HBP) calculations are reported. The effects of the different contents of the [Zn(QPhtBu)2(MeOH)2] complex on the CS biological proprieties have been evaluated, proving that the new CS@Znn films show an improved antioxidant activity, tested according to the DPPH method, with respect to pure CS, related to the concentration of the incorporated Zn(II) complex. Finally, the CS@Znn films were tried out as antimicrobial agents, showing an increase in antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus) with respect to pure CS, when detected by the agar disk-diffusion method.

ACTIVATION OF ZINC-PHOSPHATE WITH SILVER FOR ENHANCED ANTIMICROBIAL ACTIVITY

Zinc phosphate was doped with silver to enhance its antibacterial potential. The samples were prepared by coprecipitation technique in the presence of suitable surfactant and analyzed using XRD, SEM, and FTIR physicochemical techniques. The prepared sample was analyzed to assess its antibacterial properties against S. aureus and E. coli. The antifungal activity was evaluated against S. cerevisiae and A. brasiliensis and compared with that of zinc phosphate. Around a 5-fold increase in antimicrobial activity was observed with a silver activated zinc phosphate than that over the blank

An updated research on the antimicrobial properties of Chromolaena odorata (L). leaf and flower extracts against wound promoting pathogens: A comparative and combinatorial in vitro/in silico approach

The present study was aimed to evaluate and compare the antibacterial activities of Chromolaena odorata (L). leaf and flower extracts (LE and FE) against the wound promoting pathogens (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans) by a combinatorial in vitro/in silico approach. Both LE and FE was found to demonstrate increase in antimicrobial activity with increase in the concentration of the extracts, however, the activity of FE was found to non-significantly higher than the LE. These minor differences in the inhibitory action can be attributed to the variations in the phytochemical composition. The in silico molecular docking also predicted that the phytochemicals present in the LE and FE exhibited good binding with the target proteins of wound promoting pathogens. The ADME prediction studies also suggested their good pharmacokinetic and drug-likeness properties. From the present investigation, it can be inferred that both the leaves and flowers of C. odorata exhibit antibacterial activity against the wound promoting pathogens, thus aiding in wound healing process.

Rational Designed Hybrid Peptides Show up to a 6-Fold Increase in Antimicrobial Activity and Demonstrate Different Ultrastructural Changes as the Parental Peptides Measured by BioSAXS

Antimicrobial peptides (AMPs) are a promising class of compounds being developed against multi-drug resistant bacteria. Hybridization has been reported to increase antimicrobial activity. Here, two proline-rich peptides (consP1: VRKPPYLPRPRPRPL-CONH2 and Bac5-v291: RWRRPIRRRPIRPPFWR-CONH2) were combined with two arginine-isoleucine-rich peptides (optP1: KIILRIRWR-CONH2 and optP7: KRRVRWIIW-CONH2). Proline-rich antimicrobial peptides (PrAMPs) are known to inhibit the bacterial ribosome, shown also for Bac5-v291, whereas it is hypothesized a “dirty drug” model for the arginine-isoleucine-rich peptides. That hypothesis was underpinned by transmission electron microscopy and biological small-angle X-ray scattering (BioSAXS). The strength of BioSAXS is the power to detect ultrastructural changes in millions of cells in a short time (seconds) in a high-throughput manner. This information can be used to classify antimicrobial compounds into groups according to the ultrastructural changes they inflict on bacteria and how the bacteria react towards that assault. Based on previous studies, this correlates very well with different modes of action. Due to the novelty of this approach direct identification of the target of the antimicrobial compound is not yet fully established, more research is needed. More research is needed to address this limitation. The hybrid peptides showed a stronger antimicrobial activity compared to the proline-rich peptides, except when compared to Bac5-v291 against E. coli. The increase in activity compared to the arginine-isoleucine-rich peptides was up to 6-fold, however, it was not a general increase but was dependent on the combination of peptides and bacteria. BioSAXS experiments revealed that proline-rich peptides and arginine-isoleucine-rich peptides induce very different ultrastructural changes in E. coli, whereas a hybrid peptide (hyP7B5GK) shows changes, different to both parental peptides and the untreated control. These different ultrastructural changes indicated that the mode of action of the parental peptides might be different from each other as well as from the hybrid peptide hyP7B5GK. All peptides showed very low haemolytic activity, some of them showed a 100-fold or larger therapeutic window, demonstrating the potential for further drug development.

Biological and antimicrobial properties of the association Ambroxol and a water-soluble viscous liquid as a vehicle for a tricalcium silicate-based sealer

This study aimed to investigate the antimicrobial and biological properties of Ambroxol associated with glycerin (GLI), propylene glycol (PG), and polyethylene glycol (PEG) as a possible vehicle for an experimental tricalcium silicate sealer, with the intention of developing a new biomaterial. Mouse undifferentiated dental pulp cells (OD-21) were cultured, and the effects of different association on cell proliferation and inflammatory cytokine production were investigated. Antimicrobial adhesion of Enterococcus faecalis to setting sealers at 2 h was evaluated. Polyethylene tubes containing experimental sealers and empty tubes were implanted into dorsal connective tissues of 12 male 3- to 4-months-old Wistar rats (250–280 g). After 7 and 30 days, the tubes were removed and processed for histological and immunohistochemical analyses. ANOVA followed by Bonferroni correction and ANOVA followed by Tukey test was used for parametric data and Kruskal–Wallis followed by Dunn for nonparametric (p < 0.05). Cell proliferation was dose-dependent, since all association were cytotoxic at higher concentrations; however, Ambroxol–PEG showed significantly higher cytotoxicity than other association (p < 0.05). In addition, irrespective of the association, no cytokine production was observed in vitro. Ambroxol–GLI reduced bacterial viability, whereas Ambroxol–PEG increased (p < 0.05). Histological examination showed no significant difference in the inflammatory response (p > 0.05) and mineralization ability in all association. Additionally, IL-1β and TNF-α were upregulated on Ambroxol–PEG in relation to Control at 07 days (p < 0.05). Ambroxol–GLI was the best vehicle for experimental tricalcium silicate sealer, as it promoted an increase in antimicrobial activity without altering the inflammatory response or mineralization ability.

Influence of lipid bilayer composition on the activity of antimicrobial quaternary ammonium ionenes, the interplay of intrinsic lipid curvature and polymer hydrophobicity, the role of cardiolipin

Incorporation of hydrophobic component into amphiphilic polycations structure is frequently accompanied by an increase of antimicrobial activity. There is, however, a group of relatively hydrophilic polycations containing quaternary ammonium moieties along mainchain, ionenes, which also display strong antimicrobial and limited hemolytic properties. In this work, an influence of a hydrophobic side group length on antimicrobial mechanism of action is investigated in a series of novel amphiphilic ionenes. High antimicrobial activity was found by determination of minimum inhibitory concentration (MIC) and minimum bactericidal, and fungicidal concentration (MBC and MFC) in both growth media and a buffer. Biocompatibility was estimated by hemolytic and mammalian cells viability assays. Mechanistic studies were performed using large unilamellar vesicles (LUVs) with different lipid composition, as simplified models of cell membranes. The investigated ionenes are potent and selective antimicrobial molecules displaying a decrease of antimicrobial activity correlated with increase of hydrophobicity. Studies using LUVs revealed that the cardiolipin is an essential component responsible for the lipid bilayer permeabilization by investigated ionens. In contrast to relatively hydrophilic ionenes, more hydrophobic polymers showed an ability to stabilize membranes composed of lipids with negative spontaneous curvature in a certain range of polymer to lipid ratio. The results substantially contribute to the understanding of antimicrobial activity of the investigated class of polymers.

Optimization and production of antimicrobial compounds by Aspergillus flavus MTCC 13062 and its synergistic studies

The current study was focused on the antimicrobial activities of Aspergillus flavus MTCC 13062 strain isolated from solid waste dumping site, Hisar (INDIA) which showed remarkable inhibitory effect against the test organisms ( Streptococcus gordonii, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella enterica , Pseudomonas aeruginosa, Pseudomonas florescens and Candida albicans ). Response Surface Methodology (RSM) was performed to optimize the production of bioactive compounds by Aspergillus flavus MTCC 13062 which considerably increased the antimicrobial activity by 22%, 75% and 50% in E. coli , S. aureus and C. albicans, respectively at pH 7.5, temperature 28 °C and incubation period of 7 days. LC-MS was used to confirm the molecular weight and purity of the bioactive compound, while FTIR spectroscopy confirmed its structural characterization. Minimum inhibitory concentration (MIC) assay was carried out using dichloromethane extracts of Aspergillus flavus MTCC 13062 and results indicated MIC value as low as 25 μg/mL against S. aureus and E. coli while 50 μg/mL against C. albicans. Antifungal susceptibility test of Aspergillus flavus MTCC 13062 revealed that it was susceptible to Itraconazole, Fluconazole, Terbinafine, Kanamycin and Amphotericin B with zone of inhibition ranging from 10 to 24 mm . Furthermore, synergistic studies were carried out using commercial antibiotics in combination with the fungal extract and promising results were observed. We conclude that future implementation of the combinatorial results may help reduce the prescribed dosage of these antibiotics and thereby reducing the potential risks associated with the high doses of these harmful antibiotics. • A. flavus MTCC 13062 with antimicrobial potential was isolated from solid waste. • Optimization (RSM) yielded increase in antimicrobial activity by 1.1–1.7 fold. • Glycenopyrin (C 9 H 13 NO 5 ) identified as the bioactive compound using LC-MS analysis. • Purified extracts showed MIC values as 25 μg/mL against E. coli and S. aureus. • Synergism was observed on combining fungal extract with selected antibiotics.

Large-Scale Plasma Peptidomic Profiling Reveals a Novel, Nontoxic, Crassostrea hongkongensis-Derived Antimicrobial Peptide against Foodborne Pathogens.

Antimicrobial peptides are a fundamental component of mollusks’ defense systems, though they remain a thinly investigated subject. Here, infection by Vibrio parahemolyticus triggered a significant increase in antimicrobial activity in oyster plasma. By using PBS-challenged oysters as a control, plasma peptides from immunologically challenged oysters were subjected to peptidomic profiling and in silico data mining to identify bioactive peptides. Thirty-five identified plasma peptides were up-regulated post infection, among which, six up-regulated peptides (URPs) showed a relatively high positive charge. URP20 was validated with significant antibacterial activity. Virtually, URP20 triggered aggregation of bacterial cells, accompanied by their membrane permeabilization. Interestingly, URP20 was found to be active against Gram-positive and Gram-negative foodborne pathogens as well as Candida albicans, with no cytotoxicity to mammalian cells and mice. Our study provides the first large-scale plasma peptidomic dataset that identifies novel bioactive peptides in marine mollusks. Further exploration of peptide diversity in marine invertebrates should prove a fruitful pursuit for designing novel AMPs with broad applications.

Antimalarial Quinacrine and Chloroquine Lose Their Activity by Decreasing Cationic Amphiphilic Structure with a Slight Decrease in pH.

Quinacrine (QC) and chloroquine (CQ) have antimicrobial and antiviral activities as well as antimalarial activity, although the mechanisms remain unknown. QC increased the antimicrobial activity against yeast exponentially with a pH-dependent increase in the cationic amphiphilic drug (CAD) structure. CAD-QC localized in the yeast membranes and induced glucose starvation by noncompetitively inhibiting glucose uptake as antipsychotic chlorpromazine (CPZ) did. An exponential increase in antimicrobial activity with pH-dependent CAD formation was also observed for CQ, indicating that the CAD structure is crucial for its pharmacological activity. A decrease in CAD structure with a slight decrease in pH from 7.4 greatly reduced their effects; namely, these drugs would inefficiently act on falciparum malaria and COVID-19 pneumonia patients with acidosis, resulting in resistance. The decrease in CAD structure at physiological pH was not observed for quinine, primaquine, or mefloquine. Therefore, restoring the normal blood pH or using pH-insensitive quinoline drugs might be effective for these infectious diseases with acidosis.