Phylogenetically related soil actinomycetes distinguish isolation sites by their metabolic activities.

Soil environments are inhabited by microorganisms adapted to its diversified microhabitats. The metabolic activity of individual strains/populations reflects resources available at a particular spot, quality of which may not comply with broad soil characteristics. To explore the potential of individual strains to adapt to particular micro-niches of carbon sources, a set of 331 Actinomycetia strains were collected at ten sites differing in vegetation, soil pH, organic matter content and quality. The strains were isolated on the same complex medium with neutral pH and their metabolites analyzed by UHPLC and LC-MS/MS in spent cultivation medium (metabolic profiles). For all strains, their metabolic profiles correlated with soil pH and organic matter content of the original sites. In comparison, strains phylogeny based on either 16S rRNA or the beta-subunit of DNA-dependent RNA polymerase (rpoB) genes was partially correlated with soil organic matter content but not soil pH at the sites. Antimicrobial activities of strains against Kocuria rhizophila, Escherichia coli, and Saccharomyces cerevisiae were both site- and phylogeny-dependent. The precise adaptation of metabolic profiles to overall sites characteristics was further supported by the production of locally specific bioactive metabolites and suggested that carbon resources represent a significant selection pressure connected to specific antibiotic activities.

UPLC-QTOF-MS analysis of cytotoxic and antibacterial extracts of Hechtia glomerata Zucc.

Hechtia glomerata, a Mexican medicinal plant employed against bacterial infections and as food, is taxonomically related to the genus Tillandsia which has anticancer activity. Organic and aqueous extracts of H. glomerata leaves were prepared and tested for cytotoxic and antibacterial activity. UPLC-QTOF-MS analysis determined the chemical composition of active extracts to find cytotoxic and antibacterial compounds. Hexane extract was cytotoxic against HepG2, Hep3B and MCF7 (IC50: 24-28 µg/mL), whereas CHCl3/MeOH extract against PC3 and MCF7 (IC50: 25 and 32 µg/mL). CHCl3/MeOH extract showed antibacterial activity against Staphylococcus aureus and Enterococcus faecium (MIC: 125 and 62.5 µg/mL). Hexane extract cytotoxic compounds were ß-sitosterol, stigmasterol, phytol and ursolic acid. CHCl3/MeOH extract antibacterial and/or cytotoxic compounds were daucosterol, oleanolic acid, resveratrol, quercetin, kaempferol, apigenin, cyanidin, p-coumaric acid and caffeic acid. This plant could be useful against bacterial infections and cancer. However, in vivo studies are needed to determine its toxicity and therapeutic efficacy.

Immunomodulatory Effects of Allium sativum L. and its Constituents against Viral Infections and Metabolic Diseases.

BACKGROUND: Allium sativum L., or garlic, is one of the most studied plants worldwide within the field of traditional medicine. Current interests lie in the potential use of garlic as a preventive measure and adjuvant treatment for viral infections, e.g., SARS-CoV-2. Even though it cannot be presented as a single treatment, its beneficial effects are beyond doubt. The World Health Organization has deemed it an essential part of any balanced diet with immunomodulatory properties. OBJECTIVE: The aim of the study was to review the literature on the effects of garlic compounds and preparations on immunomodulation and viral infection management, with emphasis on SARS-CoV- -2. METHODS: Exhaustive literature search has been carried out on electronic databases. CONCLUSION: Garlic is a fundamental part of a well-balanced diet which helps maintain general good health. The reported information regarding garlic's ability to beneficially modulate inflammation and the immune system is encouraging. Nonetheless, more efforts must be made to understand the actual medicinal properties and mechanisms of action of the compounds found in this plant to inhibit or diminish viral infections, particularly SARS-CoV-2. Based on our findings, we propose a series of innovative strategies to achieve such a challenge in the near future.

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors.

Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata's leaves and evaluated against two cancer cell lines. The CHCl3/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.

Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics.

Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin; however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of severe life-threatening infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, Enterococcus faecium and Clostridium difficile. The expression of vancomycin Z (vanZ), encoded either in the vancomycin A (vanA) glycopeptide antibiotic resistance gene cluster or in the genomes of E. faecium, as well as Streptococcus pneumoniae and C. difficile, was shown to specifically compromise the antibiotic efficiency through the inhibition of teicoplanin binding to the bacterial surface. However, the exact mechanisms of this action and protein structure remain unknown. In this study, the three-dimensional structure of VanZ from E. faecium EnGen0191 was predicted by using the I-TASSER web server. Based on the VanZ structure, a benzimidazole based ligand was predicted to bind to the VanZ by molecular docking. Importantly, this new ligand, named G3K, was further confirmed to specifically inhibit VanZ-mediated resistance to teicoplanin in vivo.

Hechtia glomerata Zucc: Phytochemistry and Activity of Its Extracts and Major Constituents Against Resistant Bacteria.

Hechtia glomerata Zucc. is used both as a source of food and in ethnomedicine to treat various diseases derived from bacterial infections such as bronchitis, laryngitis, nephritis, whooping cough, urethritis, and sepsis. There are no previous reports about its chemistry and biological activities. Therefore, the aims of this study were to identify components from organic and aqueous extracts of H. glomerata and test the extracts and major isolate compounds against resistant bacteria. Hexane, CHCl3/MeOH, and aqueous extracts were prepared and analyzed by different chromatographic techniques. Structural elucidation was carried out by NMR spectroscopy and X-ray diffraction. The antibacterial activities of extracts, phytochemicals, and semisynthetic derivatives against resistant bacteria were determined by the broth micro-dilution method. From the hexane extract nonacosane (1), hexatriacontanyl stearate (2), hexacosanol (3), oleic acid (4), and ß-sitosterol (5) were isolated and characterized. From the CHCl3/MeOH extract, p-coumaric acid (6), margaric acid (7), caffeic acid (8), daucosterol (9), and potassium chloride (10) were isolated and characterized. A total of 58 volatile compounds were identified by GC-MS from the hexane extract and two solids were isolated from the CHCl3/MeOH extract. The UPLC-QTOF-MS analysis of the aqueous extract allowed the identification of 55 polar compounds. Hexane and aqueous extracts showed antibacterial activity against ESBL Escherichia coli, and three strains of Klebsiella pneumoniae ESBL, NDM-1 +, and OXA-48 with MIC values of 500 µg/mL. The CHCl3/MeOH extract was devoid of activity. The activity of phytocompounds and their semisynthetic derivatives toward resistant bacteria was weak. The most active compound was ß-sitosterol acetate, with a MIC value of 100 µg/mL against carbapenem-resistant A. baumannii. This is the first report of the secondary metabolites of H. glomerata Zucc. and the activity of its extracts and major pure compounds against resistant bacterial strains.