Draft genome sequence of bacterium Bacillus proteolyticus strain IMGN4 from soil.

Here, we present the draft genome of Bacillus proteolyticus IMGN4, the gram-positive, soil-dwelling bacterium discovered in mountain Maemi, Republic of Korea in May 2019. The assembly resulted in 7 contigs, comprising a total of 6,063,502 base pairs and have 6,115 coding sequences.

Synthesis of 1H-isoindolin-1-ones via a simple photodecarboxylative addition of carboxylates to phthalimides and evaluation of their antibiotic activity.

A variety of 3-hydroxy-isoindolin-1-one derivatives were synthesized using the photodecarboxylative addition of carboxylates to phthalimide derivatives in aqueous media. Subsequent acid-catalyzed dehydration furnished 3-(alkyl and aryl)methyleneisoindolin-1-ones with variable E-diastereoselectivity in good to excellent overall yields. Noteworthy, the parent 3-phenylmethyleneisoindolin-1-one underwent isomerization and oxidative decomposition when exposed to light and air. Selected 3-hydroxy-isoindolin-1-one and 3-(alkyl and aryl)methyleneisoindolin-1-one derivatives showed moderate antibacterial activity that justifies future elaboration and study of these important bioactive scaffolds.

Antibacterial Metabolites Produced by Limonium lopadusanum, an Endemic Plant of Lampedusa Island.

Lampedusa, the largest island of the Pelagie archipelago, Sicily, Italy, has proven to be a rich source of plants and shrubs used in folk medicine. These plants, often native to the island, have been very poorly investigated for their phytochemical composition and biological potential to be translated into pharmacological applications. To start achieving this purpose, a specimen of Limonium lopadusanum, a plant native to Lampedusa, was investigated for the first time. This manuscript reports the results of a preliminary biological assay, focused on antimicrobial activity, carried out using the plant organic extracts, and the isolation and chemical and biological characterization of the secondary metabolites obtained. Thus 3-hydroxy-4-methoxybenzoic acid methyl ester (syn: methyl isovanillate, (1), methyl syringate (2), pinoresinol (3), erythrinassinate C (4) and tyrosol palmitate (5) were isolated. Their antimicrobial activity was tested on several strains and compound 4 showed promising antibacterial activity against Enterococcus faecalis. Thus, this metabolite has antibiotic potential against the drug-resistant opportunistic pathogen E. faecalis.

Quality equivalence and in-vitro antibiotic activity test of different brands of amoxicillin/clavulanic acid tablets in Mwanza, Tanzania: A cross sectional study.

Background: Each film coated tablet of amoxicillin/clavulanic acid contains 500 mg of amoxicillin as an active pharmaceutical ingredient and 125 mg of clavulanic acid. Different brands have the same active ingredients but different excipients, which may cause differences in efficacy. With the emergence of generic antibiotics post-patent expiration, the antibiotic activity of generics is in question in comparison to the innovator. This study aims at determining the pharmaceutical quality and in-vitro antimicrobial activity of different brands of amoxicillin/clavulanate. Method: ology: The study was a cross-sectional laboratory-based experimental study conducted at the TMDA (Tanzania Medicines and Medical Devices Authority) Lake Zone laboratory and the CUHAS Microbiology Laboratory from in May 2021. The study samples were four brands of amoxicillin/clavulanate and sixty archived isolates, thirty of which were E. coli and the remaining thirty K. pneumoniae. Determination of minimum inhibitory concentrations, assay and dissolution test results were used to make conclusions for the study. Results: All tablets samples complied with the British pharmacopeia (BP) specifications, however sixty archived isolates which were tested in this study showed resistance towards the standard AMC disc (68 %). The innovator brand (AC1) showed significant mean difference from 2 out of 3 generics (p-values <0.05) while the first generic brand (AC2) showed significant superiority among the generics. Conclusion: Thus, the four samples that were used all complied with the specifications according to BP on dissolution and assay tests but there was an overall resistance towards amoxicillin/clavulanate, and this was moreover seen by generic brands in comparison to the innovator which proved to be of superior activity.

Multifunctional polylactic acid biocomposite film for active food packaging with UV resistance, antioxidant and antibacterial properties.

Antibacterial packaging used to control the growth of microorganisms in food is of great value for prolonging the shelf life of food. In this study, a bio-based antibacterial agent PDI based on zwitterionic and stereochemical synergistic antibacterial was designed and synthesized, and it was simultaneously introduced into polylactic acid (PLA) matrix with antioxidant o-vanillin (oVL) and plasticizer glycerol (GL). A series of PLA/oVL/PDI composite membranes with antibacterial, antioxidant and anti-ultraviolet properties were prepared by solution casting method. The results showed that the mechanical properties of the composite film were significantly improved compared with pure PLA (tensile strength increased by 37 %, elongation at break increased by 209 %), which was mainly attributed to the microphase separation structure induced by synthetic bio-based antibacterial agent, which improved the mechanical strength of PLA matrix, and the hydrogen bond formed by glycerol, o-vanillin and carbonyl group in PLA molecules plasticized PLA matrix. At the same time, the antibacterial rate of PLA/oVL/PDI composite membrane against Escherichia coli and Staphylococcus aureus can reach >95 %. Packaging experiments showed that PLA/oVL/PDI series composite films could effectively extend the shelf life of fresh bananas and apples for 5 days, and had great application prospects in preservative food packaging.

Synthesis of Schiff Bases and Secondary Amines with Indane Skeleton; Evaluation of Their Antioxidant, Antibiotic, and Antifungal Activities.

In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH4 , the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by 1 H-NMR, 13 C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC50 values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC50 values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol (4 d) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol (7 d) were determined to be 18.1 µg and 35.1 µg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.

Diversity of Culturable Bacteria from Endemic Medicinal Plants of the Highlands of the Province of Parinacota, Chile.

Endemic medicinal plants that grow at altitudes in northern Chile have been traditionally used for therapeutic applications by Aymara doctors. Several studies have analyzed the biological properties of these plants for therapeutic purposes. The aim was to characterize at molecular and biochemical levels the bacteria that live in the rhizosphere and roots from endemic medicinal plants that grow between 3681-5104 m.a.s.l. in the province of Parinacota. Thirty-nine bacteria were isolated from nine medicinal plants under our laboratory conditions. These bacteria were characterized by Gram stain, hydrolase production, plant-growth promotion, anti-fungal and antibacterial activities, and 16S rDNA sequencing. A phylogenetic study revealed the presence of three major phyla, Actinomycetota (46.2%), Bacillota (43.6%), and Pseudomonadota (10.3%). The rhizobacteria strains associated with the Aymara medicinal plant exhibited several interesting biological activities, such as hydrolytic enzymes, plant-growth-promoting traits, and antibacterial and antifungal properties, indicating their potential for developing new bio-based products for agricultural or clinical applications. These results are promising and highlight the need to point toward the search for explanations of the bio-molecular basis of the therapeutic effects of medicinal plants.

Antibacterial activity and anxiolytic-like effect of Ziziphus joazeiro Mart. leaves in adult zebrafish (Danio rerio).

Ziziphus joazeiro Mart. is an endemic plant of the Caatinga that presents a great socioeconomic importance for the Northeast and Semiarid Region of Brazil. In view of this, this study aimed to evaluate the antibacterial activity and anxiolytic-like effects of Ziziphus joazeiro Mart leaves in adult zebrafish (Danio rerio). The characterization of the main classes of metabolites was performed through chemical reactions. The antibacterial and antibiotic potentiating activity was evaluated by broth microdilution assays. The 96 h acute toxicity, open field test and anxiety models test was evaluated in vivo on adult zebrafish. The results obtained in the phytochemical prospection evidenced the presence of flobabenic tannins, leucoanthocyanidins, flavonois, flavonones, catechins, alkaloids, steroids, and triterpenoids. EEFZJ did not show antibacterial activity for all microorganism tested (MIC ≥ 1024 µg/mL), but reduced the concentration required for bacterial growth inhibition in combination with gentamicin and norfloxacin against multidrug-resistant strains of S. aureus (SA10) and E. coli (EC06), exhibiting synergistic effect with these antibiotics (p<0.0001). In the tests in vivo, EEFZJ was found to be nontoxic, performing reduced locomotor activity and demonstrated an anxiolytic-like effect in adult zebrafish via GABAergic and Serotoninergic systems (5-HT1, 5-HT2A/2C and 5-HT3A/3B).

Heat-Treated Lysozyme Hydrochloride: A Study on Its Structural Modifications and Anti-SARS-CoV-2 Activity.

Lysozyme (E.C. 3.2.1.17), an about 14 kDa protein and pI 11, widely spread in nature, is present in humans mainly in milk, saliva, and intestinal mucus as a part of innate defense mechanisms. It is endowed with antimicrobial activity due to its action as an N-acetylmuramidase, cleaving the 1-4ß glycosidic linkage in the peptidoglycan layer of Gram-positive bacteria. This antimicrobial activity is exerted only against a limited number of Gram-negative bacteria. Different action mechanisms are proposed to explain its activity against Gram-negative bacteria, viruses, and fungi. The antiviral activity prompted the study of a possible application of lysozyme in the treatment of SARS-CoV-2 infections. Among the different sources of lysozyme, the chicken egg albumen was chosen, being the richest source of this protein (c-type lysozyme, 129 amino acids). Interestingly, the activity of lysozyme hydrochloride against SARS-CoV-2 was related to the heating (to about 100 °C) of this molecule. A chemical-physical characterization was required to investigate the possible modifications of native lysozyme hydrochloride by heat treatment. The FTIR analysis of the two preparations of lysozyme hydrochloride showed appreciable differences in the secondary structure of the two protein chains. HPLC and NMR analyses, as well as the enzymatic activity determination, did not show significant modifications.

Antimicrobial Pharmacokinetics and Pharmacodynamics in Critical Care: Adjusting the Dose in Extracorporeal Circulation and to Prevent the Genesis of Multiresistant Bacteria.

Critically ill patients suffering from severe infections are prone to pathophysiological pharmacokinetic changes that are frequently associated with inadequate antibiotic serum concentrations. Minimum inhibitory concentrations (MICs) of the causative pathogens tend to be higher in intensive care units. Both pharmacokinetic changes and high antibiotic resistance likely jeopardize the efficacy of treatment. The use of extracorporeal circulation devices to support hemodynamic, respiratory, or renal failure enables pharmacokinetic changes and makes it even more difficult to achieve an adequate antibiotic dose. Besides a clinical response, antibiotic pharmacokinetic optimization is important to reduce the selection of strains resistant to common antibiotics. In this review, we summarize the present knowledge regarding pharmacokinetic changes in critically ill patients and we discuss the effects of extra-corporeal devices on antibiotic treatment together with potential solutions.

Synergistic Antibiotic Activity of Ricini Semen Extract with Oxacillin against Methicillin-Resistant Staphylococcus aureus.

Resistant bacteria are emerging as a critical problem in the treatment of bacterial infections by neutralizing antibiotic activity. The development of new traditional mechanisms of antibiotics is not the optimal solution. A more reasonable approach may be to use relatively safe, plant-based compounds in combination with conventional antibiotics in an effort to increase their efficacy or restore their activity against resistant bacteria. We present our study of mixing Ricini Semen extract, or its constituent fatty acids, with oxacillin and testing the effects of each on the growth of methicillin-resistant Staphylococcus aureus. Changes in the cell membrane fluidity of methicillin-resistant S. aureus were found to be a major component of the mechanism of synergistic antibiotic activity of Ricini Semen extract and its constituent fatty acids. In our model, changes in cellular membrane fluidity disrupted the normal function of bacterial signaling membrane proteins BlaR1 and MecR1, which are known to detect oxacillin, and resulted in the incomplete expression of penicillin-binding proteins 2a and ß-lactamase. Utilizing the mechanism presented in this study presents the possibility of developing a method for treating antibiotic-resistant bacteria using traditional antibiotics with plant-based compounds.

Antibacterial, Antifungal and Algicidal Activity of Phlorotannins, as Principal Biologically Active Components of Ten Species of Brown Algae.

Marine seaweeds synthesize a plethora of bioactive metabolites, of which phlorotannins of brown algae currently attract special attention due to their high antibiotic and cytotoxic capacities. Here we measured the minimum inhibitory concentrations (MICs) of several semi-purified phlorotannin preparations of different origins and molecular composition using a set of model unicellular organisms, such as Escherichia coli, Saccharomyces cerevisiae, Chlamydomonas reinhardtii, etc. For the first time, MIC values were evaluated for phlorotannin-enriched extracts of brown algae of the orders Ectocarpales and Desmarestiales. Phlorotannin extracts of Desmarestia aculeata, Fucus vesiculosus, and Ectocarpus siliculosus showed the lowest MIC values against most of the treated organisms (4-25 µg/mL for bacteria and yeast). Analysis of the survival curves of E. coli showed that massive loss of cells started after 3-4 h of exposure. Microalgae were less susceptible to activity of phlorotannin extracts, with the highest MIC values (≥200 µg/mL) measured for Chlorella vulgaris cells. D. aculeata, E. siliculosus, and three fucalean algae accumulate considerable amounts (4-16% of dry weight) of phlorotannins with MIC values similar to those widely used antibiotics. As these species grow abundantly in polar and temperate seas and have considerable biomass, they may be regarded as promising sources of phlorotannins.

Rejuvenating the Activity of Usual Antibiotics on Resistant Gram-Negative Bacteria: Recent Issues and Perspectives.

Antibiotic resistance continues to evolve and spread beyond all boundaries, resulting in an increase in morbidity and mortality for non-curable infectious diseases. Due to the failure of conventional antimicrobial therapy and the lack of introduction of a novel class of antibiotics, novel strategies have recently emerged to combat these multidrug-resistant infectious microorganisms. In this review, we highlight the development of effective antibiotic combinations and of antibiotics with non-antibiotic activity-enhancing compounds to address the widespread emergence of antibiotic-resistant strains.

Antibiotic Guanacastane Diterpenoids with Two New Skeletons from Psathyrella candolleana Uncovered by Semisolid and Liquid Media.

The culture of Psathyrella candolleana in host Dioscorea opposite medium produced seven new guanacastane diterpenoids, psayamin (1) as an unprecedented 5/7/6/6/6/6/7/5-fused octacyclic spiro scaffold both under liquid and semisolid conditions, psathins A-C (4-6) with a 5/7/6 tricyclic backbone by liquid medium, psathins D-E (7-8) as the same unprecedented skeletons of 5/6/7/6-fused tetracyclic or 6/7/6 tricyclic structures, and psathin F (9) with a 5/7/5/6 tetracyclic backbone by semisolid medium. The structures were elucidated by detailed spectroscopic analyses and those of 1 and 7 were determined by single-crystal X-ray crystallography. The semisolid culture led to four structure types of the guanacastane diterpenoid. Compound 5 showed antifungal activity against phytopathogen Fusarium incarnatum with a minimum inhibitory concentration (MIC) of 8 µg/mL, while compound 4 showed significant antifungal activity against Alternaria sp. with an MIC of 2 µg/mL. Compounds 1 and 8 also showed antifeedant activities against the silkworms with the feeding deterrence indices of 50%, at the concentrations of 50 µg/cm2. Compound 1 showed significant cytotoxicity with IC50 at 10.87 ± 0.24-15.96 ± 0.30 µM and anti-acetylcholinesterase activity with IC50 at 37.3 µM. Also, compound 1 remarkably induced apoptosis of HL-60 at 10, 20 µM in a concentration-dependent manner. The spiral ring of 1 was vital in cytotoxicity and anti-acetylcholinesterase activity. The different media fermented by P. candolleana resulted in the chemical diversity of bioactive guanacastane diterpenoids and potential applications in the agricultural and food functions.

Synthesis and Characterization of Calcium Alginate-Based Microspheres Entrapped with TiO2 Nanoparticles and Cinnamon Essential Oil Targeting Clinical Staphylococcus aureus.

It is important to create new generations of materials that can destroy multidrug-resistant bacterial strains, which are a serious public health concern. This study focused on the biosynthesis of an essential oil entrapped in titanium dioxide (TiO2) calcium alginate-based microspheres. In this research, calcium alginate-based microspheres with entrapped TiO2 nanoparticles and cinnamon essential oil (CI-TiO2-MSs) were synthesized, using an aqueous extract of Nigella sativa seeds for TiO2 nanoparticle preparation, and the ionotropic gelation method for microsphere preparation. The microspheres obtained were spherical, uniformly sized, microporous, and rough surfaced, and they were fully loaded with cinnamon essential oil and TiO2 nanoparticles. The synthesized microspheres were analyzed for antibacterial activity against the clinical multidrug-resistant strain of Staphylococcus aureus. Disc diffusion and flow cytometry analysis revealed strong antibacterial activity by CI-TiO2-MSs. The synthesized CI-TiO2-MSs were characterized by the SEM/EDX, X-ray diffraction, and FTIR techniques. Results showed that the TiO2 nanoparticles were spherical and 99 to 150 nm in size, whereas the CI-TiO2-MSs were spherical and rough surfaced. Apoptosis analysis and SEM micrography revealed that the CI-TiO2-MSs had strong bactericidal activity against S. aureus. The in vitro antibacterial experiments proved that the encapsulated CI-TiO2-MSs had strong potential for use as a prolonged controlled release system against multidrug-resistant clinical S. aureus.

Plant Lectins: A Review on their Biotechnological Potential Toward Human Pathogens.

The indiscriminate use of antibiotics is associated with the appearance of bacterial resistance. In light of this, plant-based products treating infections are considered potential alternatives. Lectins are a group of proteins widely distributed in nature, capable of reversibly binding carbohydrates. Lectins can bind to the surface of pathogens and cause damage to their structure, thus preventing host infection. The antimicrobial activity of plant lectins results from their interaction with carbohydrates present in the bacterial cell wall and fungal membrane. The data about lectins as modulating agents of antibiotic activity, potentiates the effect of antibiotics without triggering microbial resistance. In addition, lectins play an essential role in the defense against fungi, reducing their infectivity and pathogenicity. Little is known about the antiviral activity of plant lectins. However, their effectiveness against retroviruses and parainfluenza is reported in the literature. Some authors still consider mannose/ glucose/N-Acetylglucosamine binding lectins as potent antiviral agents against coronavirus, suggesting that these lectins may have inhibitory activity against SARS-CoV-2. Thus, it was found that plant lectins are an alternative for producing new antimicrobial drugs, but further studies still need to decipher some mechanisms of action.

Kribbellichelins A and B, Two New Antibiotics from Kribbella sp. CA-293567 with Activity against Several Human Pathogens.

Current needs in finding new antibiotics against emerging multidrug-resistant superbugs are pushing the scientific community into coming back to Nature for the discovery of novel active structures. Recently, a survey of halophilic actinomyectes from saline substrates of El Saladar del Margen, in the Cúllar-Baza depression (Granada, Spain), led us to the isolation and identification of 108 strains from the rhizosphere of the endemic plant Limonium majus. Evaluation of the potential of these strains to produce new anti-infective agents against superbug pathogens was performed through fermentation in 10 different culture media using an OSMAC approach and assessment of the antibacterial and antifungal properties of their acetone extracts. The study allowed the isolation of two novel antibiotic compounds, kribbellichelin A (1) and B (2), along with the known metabolites sandramycin (3), coproporphyrin III (4), and kribelloside C (5) from a bioassay-guided fractionation of scaled-up active extracts of the Kribbella sp. CA-293567 strain. The structures of the new molecules were elucidated by ESI-qTOF-MS/MS, 1D and 2D NMR, and Marfey's analysis for the determination of the absolute configuration of their amino acid residues. Compounds 1-3 and 5 were assayed against a panel of relevant antibiotic-resistant pathogenic strains and evaluated for cytotoxicity versus the human hepatoma cell line HepG2 (ATCC HB-8065). Kribbellichelins A (1) and B (2) showed antimicrobial activity versus Candida albicans ATCC-64124, weak potency against Acinetobacter baumannii MB-5973 and Pseudomonas aeruginosa MB-5919, and an atypical dose-dependent concentration profile against Aspergillus fumigatus ATCC-46645. Sandramycin (3) confirmed previously reported excellent growth inhibition activity against MRSA MB-5393 but also presented clear antifungal activity against C. albicans ATCC-64124 and A. fumigatus ATCC-46645 associated with lower cytotoxicity observed in HepG2, whereas Kribelloside C (5) displayed high antifungal activity only against A. fumigatus ATCC-46645. Herein, we describe the processes followed for the isolation, structure elucidation, and potency evaluation of these two new active compounds against a panel of human pathogens as well as, for the first time, the characterization of the antifungal activities of sandramycin (3).

Imidazole Derivative As a Novel Translation Inhibitor.

Searching for novel compounds with antibiotic activity and understanding their mechanism of action is extremely important. The ribosome is one of the main targets for antibiotics in bacterial cells. Even if the molecule does not suit the clinical application for whatever reasons, an investigation of its mechanism of action can deepen our understanding of the ribosome function. Such data can inform us on how the already used translational inhibitors can be modified. In this study, we demonstrate that 1-(2-oxo-2-((4-phenoxyphenyl).

Chitosan sulfate-lysozyme hybrid hydrogels as platforms with fine-tuned degradability and sustained inherent antibiotic and antioxidant activities.

The control of the properties and biological activities of chitosan-lysozyme hybrid hydrogels to exploit their interesting biomedical applications depends largely on the chitosan acetylation pattern, a difficult parameter to control. Herein, we have prepared sulfated chitosan-lysozyme hydrogels as versatile platforms with fine-tuned degradability and persistent bactericidal and antioxidant properties. The use of chitosan sulfates instead of chitosan has the advantage that the rate and mechanisms of lysozyme release, as well as antibacterial and antioxidant activities, depend on the sulfation profile, a structural parameter that is easily controlled by simple chemical modifications. Thus, while 6-O-sulfated chitosan hydrogels allow the release of loaded lysozyme in a short time (60% in 24 h), due to a high rate of degradation that allows rapid antibiotic and antioxidant activities, in 3-O-sulfated systems there is a slow release of lysozyme (80% in 21 days), resulting in long-lasting antibiotic and antioxidant activities.

Screening of biological properties of MoV2O2S2- and MoV2O4-based coordination complexes: Investigation of antibacterial, antifungal, antioxidative and antitumoral activities versus growing of Spirulina platensis biomass.

This paper deals with the biological potential of coordination compounds based on binuclear core [MoV2O2E2]2+ (E = O or S) coordinated with commercially available ligands such as oxalates (Ox2-), L-cysteine (L-cys2-), L-histidine (L-his-), Iminodiacetate (IDA2-), Nitrilotriacetate (HNTA2- or NTA3-) or ethylenediamine tetraacetate (EDTA4-) by means of various in vitro assays in a screening approach. Results suggest that the obtained complexes show weak antibacterial and antifungal properties while not being cytotoxic on cancerous and mammalian cells. In contrast, [Mo2O2E2(L-cys)2]2- complexes stand out as powerful antioxidant, whereas [Mo2O2E2(EDTA)]2- associating tetraphenylphosphonium counter-cations display strong antibiotic activity. Finally, some complexes have evidenced a positive activity towards the growing of spirulina platensis together with a modification of the proportions of biological components inside the cells. These findings reveal promising bioactivity of the bridged binuclear Mo(+V) cores inside complexes and encourage further research for new highly active yet non-toxic molecules for biological and biomedical applications.