Strategies for penicillin V dendronization with cationic carbosilane dendrons and study of antibacterial properties.

Strategies to synthesize a cationic carbosilane dendron containing the antibiotic penicillin V potassium salt (PenVK) at the focal point are discussed. The preparation of such a compound requires the use of systems with no donor atoms such as N or S in their framework, because their presence favours the rupture of the penicillin beta-lactam ring. The antibacterial activity of the new dendron containing ammonium groups, at the periphery, and the PenV moiety, at the focal point, against gram-positive Staphylococcus aureus strains was evaluated. These results were compared with those obtained for free PenVK, a related cationic dendron without a penicillin moiety at the focal point, and also compared with an equimolar mixture of this last dendron with free PenV. The data obtained indicate that, on one hand, the conjugation or interaction of PenV with cationic dendrons reduces its activity in comparison with free PenVK. On the other hand, the penicillin dendron is able to release the antibiotic in the presence of esterease, due to the breaking of the ester bond in this derivative.Ministerio de Economía y Empres

Ultrastructural Study of Acanthamoeba polyphaga Trophozoites and Cysts Treated In Vitro with Cationic Carbosilane Dendrimers

Cationic carbosilane dendrimers are branched molecules with antimicrobial properties. Their activity has been tested againstAcanthamoeba polyphaga, a causative agent ofAcanthamoebakeratitis, a severe ocular disease in humans.A. polyphagatrophozoites and cysts were exposed to different noncytotoxic cationic carbosilane dendrimers with proven antiamoebic activity. The effects of treatment on cell surface and cell ultrastructure were examined by scanning and transmission electron microscopy, respectively. Two of the dendrimers tested induced dramatic alterations of cellular ultrastructure in both trophozoites and cysts, including vacuolization, depletion of cytoplasmic contents, and reduced cell size. Additionally, we observed severe alterations of the plasma membrane with membrane blebbing in trophozoites and disruption in cysts. These alterations were also observed with chlorhexidine, a drug used for treatment ofAcanthamoebakeratitis. Our results support that these compounds may target membranes, and their action is critical for parasite integrity.Ministerio de Economía y CompetitividadComunidad de MadridJunta de Comunidades de Castilla-La Manch

Laboratory analysis of soil respiration using oxygen-sensitive microplates

Soil respiration is usually monitored by measuring CO2 efflux. Most techniques available for such kind of analyses are inconvenient and difficult to adapt to micro-method format. The present study evaluates a new microplate-based method for studying soil respiration in the laboratory. Second-generation oxygen-sensitive microplates (OSM - containing a fluorescent probe attached to the bottom of the well which provides time-resolved fluorescence data) were used to measure soil respiration either in microcosm assays or in soil water extracts. The latter procedure (water extracts) was the least cumbersome, hence it was selected for further experiments. Soil respiration curves generally showed no lag phase, starting with an exponential oxygen consumption phase, followed by a period where respiration became stable after 8-10 h of incubation at 25 ºC. Once the procedure for measurement of oxygen consumption in soil was established, the acute toxic effect of diverse chemicals on soil was analysed with OSM. Streptomycin and penicillin failed to reduce soil respiration. Kanamycin plus neomycin, trimethoprim and 5-fluorocytosine exhibited limited inhibitory effects. In contrast, some chemicals (copper sulphate and amphotericin B) and fungicides (such as dodine and fosetyl) noticeably reduced fluorescence readings, showing concentrations to give half-maximal inhibition of respiration (ICR50) ranging from 0.0064 to 0.082 g/L. Finally, some insecticides and soil amendments assayed were either neutral or increased respiration. It is concluded that OSM are reliable, convenient, and yield quantitative results. Moreover, the system is relatively inexpensive and amenable to automation. However, results obtained using soil water extracts may be different from those derived from undisturbed soil aggregates, clods or slurries studied under field conditions

In Vitro Activity of Carbosilane Cationic Dendritic Molecules on Prevention and Treatment of Candida albicans Biofilms

Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candida albicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Coleccion Espanola de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16-32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.Ministerio de Economía, Industria y CompetitividadComunidad de MadridUniversidad de Alcal

Structure-activity relationship study of cationic carbosilane dendritic systems as antibacterial agents

This work focuses on the antibacterial activity against Gram-positive Staphylococcus aureus and Gramnegative Escherichia coli and the hemolytic properties of two types of ammonium cationic carbosilane systems: dendrimers and dendrons. The effects of: i) the generation, ii) the type of peripheral groups near the cationic charges (a SiMe2 moiety or a S atom depending on the synthetic procedure, hydrosilylation or thiol-ene addition, respectively), iii) the core of dendrimers (polyphenoxo vs. Si atom) and iv) the focal point of dendrons (-N3, -NH2, -OH) have been assessed. The structure-activity relationship analysis indicates the importance of an adequate balance between the hydrophilic and lipophilic fragments of these molecules to reach the best antibacterial activity. Regarding hemolysis, lowest toxicity values were registered for dendritic systems with a sulfur atom close to the surface and, in the particular case of dendrons, for those with a hydroxyl focal point. One dendrimer and one dendron, both bearing a sulfur atom close to the surface, scored best in the activity-toxicity relationship analysis and were chosen for resistance assays. No changes in the inhibitory and bactericidal capacity in the case of the dendron and only a slight increase of these values for the dendrimer were observed after 15 subculture cycles. Furthermore, these two compounds stayed active towards different strains of resistant bacteria and avoid formation of biofilm at concentrations over the minimum inhibitory concentration (MIC).Ministerio de Economía y Empres

Antibacterial and antifungal properties of dendronized silver and gold nanoparticles with cationic carbosilane dendrons

Water soluble silver nanoparticles (AgNPs) capped with cationic carbosilane dendrons have been synthesized by direct reaction in water of dendrons, silver precursor and a reducing agent. These nanoparticles have been characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), ultraviolet spectroscopy (UV), elemental analysis, and zeta potential (ZP). The antibacterial and antifungal properties of the cationic dendrons and dendronized AgNPs and AuNPs with these dendrons have been evaluated against Gram-negative and Gram-positive bacterial -including resistant strains- and yeast strains, respectively. The results stand out for the activity of AgNPs covered with first generation dendron compared with this free dendron and corresponding dendronized AuNPs.Ministerio de Economía y Empres

Paper mill effluent decolorization by fifty Streptomyces strains.

Fifty actinomycete strains isolated from lignocellulosic substrates were examined for the ability to remove the color from a paper mill effluent obtained after semichemical alkaline pulping of wheat straw. Streptomyces sp. strains UAH 15, UAH 23, UAH 30, and UAH 51 were selected for their ability to decolorize the effluent in a liquid medium containing 1% (wt/vol) glycerol, 0.2% (wt/vol) ammonium sulfate, and 80% (vol/vol) effluent. The highest levels of decolorization achieved after the strains grew were 60 to 65%. Strains UAH 30 and UAH 51 were selected for further study because of their different patterns of effluent decolorization during growth. Fractionation of the decolorized effluent by gel permeation chromatography demonstrated that there were reductions in the levels of absorbance of the high- and medium- molecular-weight compounds. These fractions were mainly responsible for the color of the effluent, while the last fractions, the low-molecular-weight compounds, could have been responsible for the residual color of the decolorized effluent. Thin-layer chromatography revealed significant differences among the patterns of bands corresponding to the acidified supernatants obtained after precipitation of alkali-lignin from the effluent samples decolorized by different Streptomyces strains

Antibacterial Effect of Carbosilane Metallodendrimers in Planktonic Cells of Gram-Positive and Gram-Negative Bacteria and Staphylococcus aureus Biofilm

Antibiotic resistance is currently one of the main threats to public health security. Biofilm formation is a resistance mechanism that is responsible for most human bacterial infections and requires new and effective therapeutic approaches, such as those provided by nanotechnology. In this work, the antibacterial effect of carbosilane metallodendrimers with different metals (copper(II)and ruthenium(II)), ligands (chloride and nitrate) and generations (generation 0, 1 and 2) has been studied using planktonic Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Furthermore, the ability of the metallodendrimers to avoid the formation of S. aureus biofilms was also evaluated. The results showed a promising biocide activity in both types of planktonic bacteria, especially for first-generation dendrimers, which arises from the metal complexation to the dendrimer. Cu(II) metallodendrimers require lower concentration than Ru(II) counterpart to inhibit the production of S. aureus biofilms, but none produce hemolysis at the inhibitory concentrations andcan be safely used as antibacterial agents. In particular, the first-generation Cu(II) metallodendrimer with nitrate ligands displayed the most promising properties to continue with further studies in both planktonic cells and biofilms

Cationic carbosilane dendriers: influence of dendrimer framework and cationic charge on biomedical applications

Медицинская биофизик

The Antimicrobial Resistance (AMR) Rates of <i>Enterobacterales</i> in a Rural Hospital from the Eastern Region, Ghana: A Retrospective Study, 2022

Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance and often lack adequate surveillance due to a paucity of microbiological studies. In this 2022 study, our goal was to contribute to a more precise antimicrobial treatment by understanding the prevalence of resistance in a rural environment, promoting antibiotic stewardship, and raising awareness about antimicrobial resistance. We assessed the prevalence of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Enterobacterales in clinical samples from 2905 patients being treated at Saint Dominic’s Hospital, Akwatia, in the countryside of the Eastern Region, Ghana, in the year 2022. To this purpose, the samples were cultured on agar plates prepared in the laboratory using purified Oxoid™ Thermo Scientific™ agar (Thermo Fisher Scientific; Waltham, MA, USA). Cystine Lactose Electrolyte-Deficient (CLED) agar was used for urine samples, while blood agar, chocolate agar, and MacConkey agar were used for the rest of the specimens tested (HVS, blood, BFA, sputum). Antimicrobial susceptibility was determined on site using the disc diffusion method (Kirby-Bauer test). MDR bacteria accounted for more than half (53.7%) of all microorganisms tested for three or more antibiotics and 37.3% of these were XDR. Multivariate regression analysis was performed to identify risk factors associated with acquiring MDR/XDR bacteria. The results showed an increased likelihood of MDR acquisition linked to being male (OR 2.39, p p = 0.027 for XDR), higher age (OR 1.01, p = 0.049 for MDR), non-sputum samples (OR 0.32, p = 0.009 for MDR), and urine samples (OR 7.46, p < 0.001 for XDR). These findings emphasize the urgency for surveillance and control of antimicrobial resistance; to this end, making accurate diagnostics, studying the microorganism in question, and conducting susceptibility testing is of the utmost importance