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Antimicrobial resistance has attracted worldwide attention and remains an urgent issue to resolve. Discovery of novel compounds is regarded as one way to circumvent the development of resistance and increase the available treatment options. Gossypol is a natural polyphenolic aldehyde, and it has attracted increasing attention as a possible antibacterial drug. In this paper, we studied the antimicrobial properties (minimum inhibitory concentrations) of gossypol acetate against both Gram-positive and Gram-negative bacteria strains and dig up targets of gossypol acetate using in vitro assays, including studying its effects on functions (GTPase activity and polymerization) of Filamenting temperature sensitive mutant Z (FtsZ) and its interactions with FtsZ using isothermal titration calorimetry (ITC), and in vivo assays, including visualization of cell morphologies and proteins localizations using a microscope. Lastly, Bacterial membrane permeability changes were studied, and the cytotoxicity of gossypol acetate was determined. We also estimated the interactions of gossypol acetate with the promising target. We found that gossypol acetate can inhibit the growth of Gram-positive bacteria such as the model organism Bacillus subtilis and the pathogen Staphylococcus aureus [both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA)]. In addition, gossypol acetate can also inhibit the growth of Gram-negative bacteria when the outer membrane is permeabilized by Polymyxin B nonapeptide (PMBN). Using a cell biological approach, we show that gossypol acetate affects cell division in bacteria by interfering with the assembly of the cell division FtsZ ring. Biochemical analysis shows that the GTPase activity of FtsZ was inhibited and polymerization of FtsZ was enhanced in vitro, consistent with the block to cell division in the bacteria tested. The binding mode of gossypol acetate in FtsZ was modeled using molecular docking and provides an understanding of the compound mode of action. The results point to gossypol (S2303) as a promising antimicrobial compound that inhibits cell division by affecting FtsZ polymerization and has potential to be developed into an effective antimicrobial drug by chemical modification to minimize its cytotoxic effects in eukaryotic cells that were identified in this work. [ABSTRACT FROM AUTHOR]

Electro-generation of RuIV=O species from the RuII-aqua complex is a crucial step to excel the electrocatalytic water oxidation performance of ruthenium oxo complexes. We report herein the synthesis and X-ray crystal structural characterizations of new RuII-aqua complexes containing N-substituted 2,2'-dipyridylamine ligands (L) tagged with an alkyl chain of various lengths, [Ru(tpy)(L)(OH2)]2+. Cyclic voltammetric analyses show that the length of the alkyl chain exerts great influence on the electro-generation of RuIV=O species. The L with a longer alkyl chain in an acidic aqueous medium promotes the conversion of RuIII-OH to RuIV=O efficiently. Surprisingly, this conversion can be further enhanced by the presence of perchlorate anions. Chronocoulometric data reveal that the alkyl chain on L promotes the adsorption of the ruthenium complex on the electrode surface. Bulk electrolysis results indicate that the [Ru(tpy)(dppa)(OH2)]2+ (dppa=(2,2'-dipyridyl)-n-propylamine) gives the most active electrocatalytic water oxidation activity among the ruthenium-aqua complexes investigated in this study. [ABSTRACT FROM AUTHOR]

Tachyplesin I is a potent antimicrobial peptide with broad spectrum of antimicrobial activity. It has 2 disulfide bonds and can form 3 disulfide bond isomers. In this study, the structure and antimicrobial activity of 3 tachyplesin I isomers (tachyplesin I, 3C12C, 3C7C) were investigated using molecular dynamic simulations, circular dichroism structural study, as well as antimicrobial activity and hemolysis assay. Our results suggest that in comparison to the native peptide, the 2 isomers (3C12C, 3C7C) have substantial structural and activity variations. The native peptide is in the ribbon conformation, while 3C12C and 3C7C possess remarkably different secondary structures, which are referred as "globular" and "beads" isomers, respectively. The substantially decreased hemolysis effects for these 2 isomers is accompanied by significantly decreased anti-gram-positive bacterial activity. [ABSTRACT FROM AUTHOR]

Electrical interactions between bacteria and the environment are delicate and essential. In this study, an external electrical current is applied to capacitive titania nanotubes doped with carbon (TNT-C) to evaluate the effects on bacteria killing and the underlying mechanism is investigated. When TNT-C is charged, post-charging antibacterial effects proportional to the capacitance are observed. This capacitance-based antibacterial system works well with both direct and alternating current (DC, AC) and the higher discharging capacity in the positive DC (DC+) group leads to better antibacterial performance. Extracellular electron transfer observed during early contact contributes to the surface-dependent post-charging antibacterial process. Physiologically, the electrical interaction deforms the bacteria morphology and elevates the intracellular reactive oxygen species level without impairing the growth of osteoblasts. Our finding spurs the design of light-independent antibacterial materials and provides insights into the use of electricity to modify biomaterials to complement other bacteria killing measures such as light irradiation. [ABSTRACT FROM AUTHOR]

The prevalence of multidrug resistance among clinically significant bacteria calls for the urgent development of new antibiotics with novel mechanisms of action. In this study, a new small molecule exhibiting excellent inhibition of bacterial cell division with potent antibacterial activity was discovered through cell-based screening. The compound exhibits a broad spectrum of bactericidal activity, including the methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli. The in vitro and in vivo results suggested that this compound disrupts the dynamic assembly of FtsZ protein and Z-ring formation through stimulating FtsZ polymerization. Moreover, this compound exhibits no activity on mammalian tubulin polymerization and shows low cytotoxicity on mammalian cells. Taken together, these findings could provide a new chemotype for development of antibacterials with FtsZ as the target. [ABSTRACT FROM AUTHOR]

Novel hairpin DNA probes are designed and constructed based on target-induced in situ generation of luminescent silver nanoclusters. This design allows specific and versatile detection of diverse targets with easy operation and low cost. [ABSTRACT FROM AUTHOR]

Background: β-lactamase conjugated with environment-sensitive fluorescein molecule to residue 166 on the ∩-loop near its catalytic site is a highly effective biosensor for β-lactam antibiotics. Yet the molecular mechanism of such fluorescence-based biosensing is not well understood. Results: Here we report the crystal structure of a Class A β-lactamase PenP from Bacillus licheniformis 749/C with fluorescein conjugated at residue 166 after E166C mutation, both in apo form (PenP-E166Cf) and in covalent complex form with cefotaxime (PenP-E166Cf-cefotaxime), to illustrate its biosensing mechanism. In the apo structure the fluorescein molecule partially occupies the antibiotic binding site and is highly dynamic. In the PenPE166Cf- cefatoxime complex structure the binding and subsequent acylation of cefotaxime to PenP displaces fluorescein from its original location to avoid steric clash. Such displacement causes the well-folded ∩-loop to become fully flexible and the conjugated fluorescein molecule to relocate to a more solvent exposed environment, hence enhancing its fluorescence emission. Furthermore, the fully flexible ∩-loop enables the narrow-spectrum PenP enzyme to bind cefotaxime in a mode that resembles the extended-spectrum β-lactamase. Conclusions: Our structural studies indicate the biosensing mechanism of a fluorescein-labelled β-lactamase. Such findings confirm our previous proposal based on molecular modelling and provide useful information for the rational design of β-lactamase-based biosensor to detect the wide spectrum of β-lactam antibiotics. The observation of increased ∩-loop flexibility upon conjugation of fluorophore may have the potential to serve as a screening tool for novel β-lactamase inhibitors that target the ∩-loop and not the active site. [ABSTRACT FROM AUTHOR]

Carbohydrate microarrays have attracted increasing attention in recent years because of their ability to monitor biologically important protein–carbohydrate interactions in a high-throughput manner. Here we have developed an effective approach to immobilizing intact carbohydrates directly on polystyrene microtiter plates coated with amine-functionalized sol–gel monolayers. Lectin binding was monitored by fluorescence spectroscopy using these covalent arrays of carbohydrates that contained six mono- and di-saccharides on the microplates. In addition, binding affinities of lectin to carbohydrates were also quantitatively analyzed by determining IC50values of lectin-specific antibody with these arrays. Our results indicate that microplate-based carbohydrate arrays can be efficiently fabricated by covalent immobilization of intact carbohydrates on sol–gel-coated microplates. The microplate-based carbohydrate arrays can be applied for screening of protein–carbohydrate interactions in a high-throughput manner. [ABSTRACT FROM AUTHOR]

A new molecular beacon (MB) driven by two-photon excitation (TPE) using quantum dots as energy donor is constructed, which provides reduced direct excitation of acceptor and is free of interferences from autofluorescence or scattering light in a complicated biological matrix. [ABSTRACT FROM AUTHOR]

A novel Re(i) complex covalently anchored with a pyrrolidinium moiety was successfully synthesized and used as an efficient and recyclable catalyst in the cycloaddition of CO2 with epoxides under mild reaction conditions to give excellent isolated yield and selectivity of cyclic carbonates in pyrrolidinium ionic liquid. [ABSTRACT FROM AUTHOR]