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Vulvovaginal candidiasis (VVC) is a most common infection caused by Candida species especially, Candida albicans. Herein, we report that phytoprotein based nano scaffolds mitigates the standard antifungal drug (fluconazole) resistant C. albicans. Copper sulfide nanoparticles (CuS NPs) and the phytolectin, jacalin functionalized copper sulfide nanoparticles (JCuS NPs) were evaluated against C. albicans cells. The minimum inhibitory concentration of JCuS NPs (0.1 µM) was tenfold lower than CuS NPs (1 µM). Kill curve assay showed that the NPs exhibit anticandidal activity in a time dependent manner. Standard antifungal drugs like Amphotericin B (AMP B) and Micafungin (MF) were evaluated individually against VVC causing Candida sp. and also combined with NPs to determine their synergistic effect. Interestingly, MF which belongs to echinocandins group of antifungals exhibhited synergistic activity and AMP B which belongs to polyenes group displayed an additive effect. Molecular level studies revealed that JCuS NPs in combination with micafungin inhibits the drug resistant efflux pump of C. albicans by down-regulating the efflux genes. The results revealed that JCuS NPs and its combination with standard drugs have a better anti-candidal effect, suggesting that the lectins has the potential to serve as a drug carrier by targeting the cell surface glycans of Candida.

The emergence of drug-resistant microorganisms and the failure of conventional antibiotics demand extensive research efforts to develop more effective antimicrobial therapies. A new series of cationic N-acylethanolamines was synthesized through introducing a (2-methylene-1-methylpyridinium iodide) moiety, and their antimicrobial activity was evaluated against Mycobacterium smegmatis. The minimum inhibitory concentration (MIC) of cNAEs follows a fourfold decrement when the N-acyl chain length increases by two methylene units. Inspiringly, the lowest MIC of 15.63 μM was observed with 2-((N-(2-hydroxyethyl)palmitamido)methyl)-1-methylpyridin-1-ium iodide, suggesting the necessity of a hydrophilic–lipophilic balance for better antimicrobial activity. cNAEs are unique, because they do not produce reactive oxygen species as most antibiotics do, but exert antimicrobial activity through loss of membrane integrity and membrane depolarization. Further, cNAEs and their combination with a standard drug, isoniazid, exhibit synergistic activity at lower concentrations (cN16E/INH – 3.91/1.95 μM) in comparison to the MIC of the individual drug. Strikingly, the combination showed a bactericidal effect through bacterial membrane disruption, ROS generation and membrane depolarization. Notably, a hemolytic study showed that cN16E is nontoxic to human red blood cells, even above 100 fold higher MIC. The result signifies that cN16E can be used as a potential drug against mycobacteria, as well as in combination with other antimycobacterial drugs.

Aim Polymicrobial biofilm encasing cross-kingdom micro-organisms are apparent in medicine, which imposes serious resistance to conventional antimicrobial treatment. The objective of the study was to explore Butea monosperma seed lectin (BMSL) conjugated antimicrobial lipid, 2-((N-[2-hydroxyethyl]palmitamido)methyl)-1-methylpyridin-1-ium iodide (cN16E) to inhibit mixed-species biofilm of uropathogenic Escherichia coli–Candida albicans. Methods and Results Antimicrobial activity and antibiofilm of cN16E and cN16E-BMSL conjugate (BcN16E) were analysed against single- and mixed microbial cultures. The minimum inhibitory concentration (MIC) indicates that the MIC of cN16E-BMSL conjugate (BcN16E) against cohabiting UPEC-C. albicans was eightfold lower than the cN16E. BcN16E affects membrane integrity to elicit antimicrobial activity. BcN16E inhibits the dual-species biofilm even with 16 times lower MIC of cN16E. BcN16E impairs the biofilm-associated virulence factors which include extracellular polysaccharides, cell surface hydrophobicity, swimming, swarming motilities, hyphal filamentous morphology, curli formation and haemolysin activity. As a proof of concept, we demonstrated BcN16E ability to inhibit dual-species biofilm formation on a urinary catheter. Conclusion The study revealed that the BcN16E is better than cN16E in impairing biofilm-associated virulence factors and exerting antimicrobial activity. Significance and Impact of the Study The findings emphasize that phytolectin has the potential to enhance the anti-virulence strategies of antimicrobials against cross-kingdom biofilm-related infections.

N-acyltaurines (NATs) are biologically active amphiphilic lipids. They come under the group of compounds known as N-acyl amino acids. NATs were first detected in the brain and other tissues in mice lacking the enzyme fatty acid amide hydrolase FAAH (-/-). N-arachidonoyltaurine (20:4 NAT) acts as an excellent ligand for the subset of transient receptor potential (TRP) channels, especially vanilloid type channels TRPV1 and TRPV4. Also, hydrophobic and hydrophilic regions of NATs enable them to interact with membrane lipids. Here, we have investigated the interaction of NATs, N-myristoyltaurine (NMT), and N-palmitoyltaurine (NPT) with their corresponding diacyl phosphatidylcholines (PCs), dimyristoylphosphatidylcholine (DMPC), and dipalmitoylphosphatidylchoine (DPPC). The miscibility and phase behavior of the hydrated binary mixtures have been investigated by differential scanning calorimetry (DSC). Studies on the interaction of NMT/NPT with DMPC/DPPC revealed that the two amphiphiles mix well up to 50 mol% of NAT and phase separation is observed at higher contents of the NAT. The phase transition of the equimolar mixtures of NAT:PC (50:50) studied by fluorescence, also supported the DSC results. PXRD and FTIR analysis show that the NAT:PC equimolar mixture (50:50) forms different supramolecular structures when compared to that of individual NATs and PCs. From transmission electron microscopic studies it is observed that the equimolar mixtures of NMT and NPT with their corresponding diacylphosphatidylcholines (50:50, mol/mol) forms unilamellar vesicles whose diameter range between 30 and 50 nm.

Vulvovaginal candidiasis (VVC) is a commonly occurring yeast infection caused by Candida species in women. Among Candida species, C. albicans is the predominant member that causes vaginal candidiasis followed by Candida glabrata. Biofilm formation by Candida albicans on the vaginal mucosal tissue leads to VVC infection and is one of the factors for a commensal organism to get into virulent form leading to disease. In addition to that, morphological switching from yeast to hyphal form increases the risk of pathogenesis as it aids in tissue invasion. In this study, jacalin, a phytolectin complexed copper sulfide nanoparticles (NPs) have been explored to eradicate the mono and mixed species biofilms formed by fluconazole-resistant C. albicans and C. glabrata isolated from VVC patients. NPs along with standard antifungals like micafungin and amphotericin B have been evaluated to explore interaction behavior and we observed synergistic interactions between them. Microscopic techniques like light microscopy, phase contrast microscopy, scanning electron microscopy, confocal laser scanning microscopy were used to visualize the inhibition of biofilm by NPs and in synergistic combinations with standard antifungals. Real-time PCR analysis was carried out to study the expression pattern of the highly virulent genes which are responsible for yeast to hyphal switch, drug resistance and biofilm formation upon treatment with NPs in combination with standard antifungals. The current study shows that lectin-conjugated NPs with standard antifungals might be a different means to disrupt the mixed species population of Candida spp. that causes VVC. Lay Summary The present study focuses on exploiting the high biding affinity between the cell surface glycans present in Candida cells and the plant lectin, Jacalin. Jacalin serves as a ‘Trojan Horse’ wherein the lectin-coupled nanoparticles show a high efficacy when compared with the unconjugated nanoparticles. The present approach also improves the anti-biofilm activity of the antifungal drugs against drug-resistant Candida strains.

Lectins are known for their ability to bind to cell surface glycans, and are useful to develop a glycan-targeted drug delivery system. This study aimed to evaluate the capacity of pectin capped copper sulfide nanoparticles (pCuS NPs) to modulate the antibacterial activity of a lectin, Md-Lec, purified from the shrimp, Metapenaeus dobsoni. Fluorescence spectroscopy revealed that Md-Lec has the ability to form a complex with pCuS NPs. Haemagglutination assay showed that the carbohydrate binding site of the lectin was preserved even after complexing with pCuS. The minimum inhibitory concentrations (MICs) obtained for Md-Lec and pCuS NPs against the tested aquatic pathogens were 50 μg ml−1 and 12.5 μM, respectively. Interestingly, the MIC of Md-Lec–pCuS NPs complex was four fold lower than that of pCuS, which was attributed to the bacterial cell surface glycan recognization activity of Md-Lec. Zone of inhibition assay showed that the zone size was highest for the lectin conjugated nanoparticles. Mechanistic study revealed that Md-Lec–pCuS NPs affect the bacterial membrane integrity and produce a large volume of reactive oxygen species to kill the bacteria. The practical aspect of using this lectin–pCuS NPs complex was evaluated by treating bacteria infected Nile tilapia (Oreochromis niloticus). The bacterial load was much less in the lectin–pCus NPs complex treated fish; moreover, the fish fully recovered from the infection. It was concluded that the conjugate of antibacterial lectin and NPs is more effective than the individual components.

The discharge of organic dyes and hazardous heavy metals from diverse industries into the environment has become a serious problem. Herein, we report that N-myristoyltaurine capped copper nanoparticles (CuNPs) speeds up the decolorization of dye effluents in the presence of sodium borohydride (NaBH4). The decolorization followed by UV–visible spectroscopy revealed that the reaction follows pseudo first-rate kinetics. All the tested dyes decolorized in less than 3 min. As a result of decolorization, the toxicity of the dye effluents decrease considerably, which was proved by seed germination assay. Further, the surface plasmon resonance property of the CuNPs was explored for selective and sensitive detection of hazardous mercury ions in sewage water (SW) and artificial cerbospinal fluid (aCSF). In the presence of Hg2+, galvanic displacement reactions promote the aggregation and the color change of CuNPs from wine red to grayish white. On the basis of colorimetric change, a minimum concentration of 15 μM of Hg2+ can be detected by the naked eye. The spectrophotometric detection method showed a detection limit of 0.1125 μM. Interference studies suggest that CuNPs is highly sensitive to Hg2+ ions. Recovery experiments proved that CuNPs quantitatively detect the spiked Hg2+ ions in tap water, SW and aCSF with an acceptable recovery range of 92 to 113%. Overall, the experimental outcomes suggest that the CuNPs could be deployed as a catalyst to decolorize dye effluents and as a colorimetric probe for mercury detection in wastewater.

Herein, a natural sunlight mediated synthesis of gold nanoparticles (AuNPs) using escin, a triterpenoid glycoside was reported for the first time. Transmission electron microscopy imaging revealed that the size of escin stabilized AuNPs falls within the range of 5–20 nm and their surface plasmon resonance maximum was observed at 530 nm. Escin-AuNPs was found to improve insulin-dependent glucose uptake in L6 rat skeletal muscle cells, which was further confirmed by estimating the stored glycogen content. Escin-AuNPs exhibited excellent free radical scavenging activity. Thus, escin-AuNPs may be considered as promising molecule to test against diabetic complications.

Designer micellar medium was explored for the transformation of diverse anilines to the corresponding densely substituted biologically relevant skatole derivatives in an aqueous medium via 5-exo-trig cyclization reaction. The scope of the reaction was extended to intermolecular Csp2-Csp2 and Csp2-N bond forming reactions in water. Systematic investigations revealed that altering hydrophobicity of surfactant influences the yield of both C C and C N bond forming reactions in water.

A simple single-stage method, based on refluxing edible carrot with aqueous trisodium phosphate (TSP) has been reported to synthesize blue color luminescent carbon dots (CDs). Transmission electron microscopy (TEM) image showed that CDs are almost spherical in shape and the size is around 3–8 nm. Fourier-transform infrared (FTIR) and 1H NMR spectroscopy study revealed that the carbohydrates present in the carrot undergone carbonization to produce luminescent CDs. Optimization study indicate that refluxing 5 g of carrot in 80 mM TSP aqueous solution for 120 min is adequate to produce highly luminescent blue CDs. The CDs produced are used as luminophore to image bacteria through fluorescence microscopy. CDs have membrane good permeability and minimum toxicity against Gram-negative and Gram-positive bacteria. The CDs capability for direct reduction of silver ions to elemental silver (Ag0) and gold ions to elemental gold (Au0) without additional reducing and stabilizing agent was demonstrated. The resulting Ag and Au nanoparticles have a size of 8–22 nm and 5–15 nm, respectively. The catalytic activity of nanoparticles in the hydrogenation reaction was investigated. The results suggest that the nanoparticles had high catalytic activity in the sodium borohydride mediated hydrogenation of nitroaromatic compounds.

In this paper, the application of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) synthesized using a biomimetic lipid, N-myristoyltaurine (N14T) was evaluated in common fields. The catalytic effectiveness of AgNPs and AuNPs was studied in the popular nanocatalyst reaction, nitroaromatic reduction, and dye degradation. Both NPs display catalytic activity in the nitroaromatic compound and organic dyes reduction reaction involving sodium borohydride and the rate constant is estimated as 10

The disposition of a drug in a biological system may be altered by complex biological fluids; especially, protein binding to drugs influences their activity. Herein, we demonstrated a convenient method involving the noncovalent formulation of butea monosperma seed lectin (BMSL) with an antimicrobial lipid, cationic N-acylethanolamine (cNAE) to mitigate the serum protein interference. Fluorescence spectroscopy and molecular docking study revealed that cNAEs readily formed noncovalent complexes with serum protein, bovine serum albumin. The resulting complexes interfered with the antimicrobial activity of cNAEs. Strikingly, the noncovalent conjugates developed with BMSL and cNAEs (BcNAE) overcame the interference from serum protein and displayed remarkable antimicrobial activity against uropathogenic Escherichia coli (UPEC). Strikingly, the minimum inhibitory concentration (MIC) of the lectin conjugates (7.81 μM) was 4-fold lower than the MIC of pure cNAE. Mechanistic studies showed that BcNAE depolarized the bacterial membrane and affected the integrity to exert the antimicrobial activity. The membrane directed activities of BcNAE on UPEC efficiently eliminated the development of resistance even after 25 passages. The hemocompatibility results and the biosafety assessed in a zebrafish model suggested that BcNAE was nontoxic with good selectivity to bacteria. While testing the therapeutic efficacy against UPEC infected zebrafish, we found that 1× MIC cNAE is ineffective due to interference from biological fluids, which is in agreement with in vitro studies. Remarkably, the infected fish treated with 1× MIC BcNAE conjugates were rescued from infection and restored to the normal life in less than 9 h. Bacterial colony count assay revealed that BcNAE was more efficient in overcoming the biological fluid interference and eliminated the bacterial burden in infected zebrafish. Histopathology analysis supported that BcNAE treatment restored the pathological changes induced by UPEC and, thus, increased survival. The high antimicrobial intensity with limited chance for resistance development and potential to overcome biomolecular interference with a lack of toxicity enhance the merits of exploring lectin conjugates against infectious pathogens.