The potential of dietary nanoparticles to enhance allergenicity of milk proteins: an in vitro investigation.

In recent years, the popularity of dietary nanoparticles (NPs) in the food industry as additives has raised concerns because of the lack of knowledge about potential adverse health outcomes ensuing from the interactions of NPs with components of the food matrix and gastrointestinal system. In this study, we used a transwell culture system that consisted of human colorectal adenocarcinoma (Caco-2) cells in the apical insert and Laboratory of Allergic Diseases 2 mast cells in the basal compartment to study the effect of NPs on milk allergen delivery across the epithelial layer, mast cell responses and signaling between epithelial and mast cells in allergenic inflammation. A library of dietary particles (silicon dioxide NPs, titanium dioxide NPs and silver NPs) that varied in particle size, surface chemistry and crystal structures with or without pre-exposure to milk was used in this investigation. Milk-interacted particles were found to acquire surface corona and increased the bioavailability of milk allergens (casein and ß-lactoglobulin) across the intestinal epithelial layer. The signaling between epithelial cells and mast cells resulted in significant changes in the early phase and late-phase activation of the mast cells. This study suggested that antigen challenge in mast cells with the presence of dietary NPs may cause the transition of allergic responses from an immunoglobulin E (IgE)-dependent mechanism to a mixed mechanism (both IgE-dependent and IgE-independent mechanisms).

Genomic and phenotypic profiling of Staphylococcus aureus isolates from bovine mastitis for antibiotic resistance and intestinal infectivity.

BACKGROUND: Staphylococcus aureus is one of the prevalent etiological agents of contagious bovine mastitis, causing a significant economic burden on the global dairy industry. Given the emergence of antibiotic resistance (ABR) and possible zoonotic spillovers, S aureus from mastitic cattle pose threat to both veterinary and public health. Therefore, assessment of their ABR status and pathogenic translation in human infection models is crucial. RESULTS: In this study, 43 S. aureus isolates associated with bovine mastitis obtained from four different Canadian provinces (Alberta, Ontario, Quebec, and Atlantic provinces) were tested for ABR and virulence through phenotypic and genotypic profiling. All 43 isolates exhibited crucial virulence characteristics such as hemolysis, and biofilm formation, and six isolates from ST151, ST352, and ST8 categories showed ABR. Genes associated with ABR (tetK, tetM, aac6', norA, norB, lmrS, blaR, blaZ, etc.), toxin production (hla, hlab, lukD, etc.), adherence (fmbA, fnbB, clfA, clfB, icaABCD, etc.), and host immune invasion (spa, sbi, cap, adsA, etc.) were identified by analyzing whole-genome sequences. Although none of the isolates possessed human adaptation genes, both groups of ABR and antibiotic-susceptible isolates demonstrated intracellular invasion, colonization, infection, and death of human intestinal epithelial cells (Caco-2), and Caenorhabditis elegans. Notably, the susceptibilities of S. aureus towards antibiotics such as streptomycin, kanamycin, and ampicillin were altered when the bacteria were internalized in Caco-2 cells and C. elegans. Meanwhile, tetracycline, chloramphenicol, and ceftiofur were comparatively more effective with ≤ 2.5 log10 reductions of intracellular S. aureus. CONCLUSIONS: This study demonstrated the potential of S. aureus isolated from mastitis cows to possess virulence characteristics enabling invasion of intestinal cells thus calling for developing therapeutics capable of targeting drug-resistant intracellular pathogens for effective disease management.

Mechanistic study of the increased phototoxicity of titanium dioxide nanoparticles to Chlorella vulgaris in the presence of NOM eco-corona.

Widespread applications and release of photoactive nanoparticles (NPs) such as titanium dioxide (TiO2) into environmental matrices warrant mechanistic investigations addressing toxicity of NPs under environmentally relevant conditions. Accordingly, we investigated the effects of surface adsorbed natural organic matters (NOMs) such as humic acid, tannic acid and lignin on the band gap energy, abiotic reactive oxygen species (ROS) generation, surface chemistry and phototoxicity of TiO2 NPs. Initially, a liquid assisted grinding method was optimized to produce TiO2 NPs with a NOM layer of defined thickness for further analysis. Generally, adsorption of NOM reduced the band-gap energy of TiO2 NPs from 3.08 eV to 0.56 eV with humic acid, 1.92 eV with tannic acid and 2.48 eV with lignin. Light activated ROS generation by TiO2 NPs such as hydroxyl radicals, however, was reduced by 4, 2, 9 times in those coated with humic acid, tannic acid and lignin, respectively. This reduction in ROS despite decrease in band gap energy corroborated with the decreased surface oxygen vacancy (as revealed by X-ray Photoelectron Spectroscopy (XPS)) and quenching of ROS by surface adsorbed NOM. Despite the reduced ROS generation, the NOM-modified TiO2 NPs exhibited an increased phototoxicity to Chlorella vulgaris in comparison to pristine TiO2 NPs. Further analysis suggested that photoactivation of NOM modified TiO2 NPs releases toxic degradation products. Findings from our studies thus provide mechanistic insight into the ecotoxic potential of NOM-modified TiO2 NPs when exposed to light in the environment.

Hazard Profiling of Commercially Relevant Quantum Dot Components Revealed Synergistic Interactions between Heavy Metals and Polymers.

Commercially used quantum dots (QDs) exemplify complex nanomaterials with multiple components, though little is known about the type of interactions between these components in determining the overall toxicity of this material. We synthesized and characterized a functional QD (CdSe/ZnS_P&E) that was identical in structure and composition to a patented and commercially applied QD and the combinations of its components (CdSe, CdSe/ZnS, ZnS, CdSe_P&E, ZnS_P&E, and P&E). Cells exposed to incremental concentrations of these materials were investigated for cell viability and cellular perturbations, contributing to a final common pathway of cell death using high-content screening assays in model human intestinal epithelial cells (HIEC-6). The concentrations that resulted in a loss of 20% cell viability (EC20 values) for each tested component were used for estimating the combination index (CI) to evaluate synergistic or antagonistic effects between the components. Complete QD (core/shell-polymer) showed the highest toxic potential due to synergistic interactions between core and surface functional groups. The cationic polymer coating enhanced cellular uptake of the QD, ensuing lysosome acidification and release of heavy metal ions to the intracellular milieu, and caused oxidative stress and cytotoxicity. Overall, this study advances our understanding of the collective contribution of individual components of a functional QD toward its toxic potential and emphasizes the need to study multilayered nanomaterials in their entirety for hazard characterization.

Prevalence and mechanisms of antibiotic resistance in Escherichia coli isolated from mastitic dairy cattle in Canada.

BACKGROUND: Bovine mastitis is the most common infectious disease in dairy cattle with major economic implications for the dairy industry worldwide. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from dairy farms is vital not only for animal husbandry but also for public health. METHODS: In this study, the prevalence of AMR in 113 Escherichia coli isolates from cases of bovine clinical mastitis in Canada was investigated. Kirby-Bauer disk diffusion test with 18 antibiotics and microdilution method with 3 heavy metals (copper, zinc, and silver) was performed to determine the antibiotic and heavy-metal susceptibility. Resistant strains were assessed for efflux and ß-lactamase activities besides assessing biofilm formation and hemolysis. Whole-genome sequences for each of the isolates were examined to detect the presence of genes corresponding to the observed AMR and virulence factors. RESULTS: Phenotypic analysis revealed that 32 isolates were resistant to one or more antibiotics and 107 showed resistance against at least one heavy metal. Quinolones and silver were the most efficient against the tested isolates. Among the AMR isolates, AcrAB-TolC efflux activity and ß-lactamase enzyme activities were detected in 13 and 14 isolates, respectively. All isolates produced biofilm but with different capacities, and 33 isolates showed α-hemolysin activity. A positive correlation (Pearson r = + 0.89) between efflux pump activity and quantity of biofilm was observed. Genes associated with aggregation, adhesion, cyclic di-GMP, quorum sensing were detected in the AMR isolates corroborating phenotype observations. CONCLUSIONS: This investigation showed the prevalence of AMR in E. coli isolates from bovine clinical mastitis. The results also suggest the inadequacy of antimicrobials with a single mode of action to curtail AMR bacteria with multiple mechanisms of resistance and virulence factors. Therefore, it calls for combinatorial therapy for the effective management of AMR infections in dairy farms and combats its potential transmission to the food supply chain through the milk and dairy products.

New Trends in the Microencapsulation of Functional Fatty Acid-Rich Oils Using Transglutaminase Catalyzed Crosslinking.

Preparing stable protein-based microcapsules containing functional fatty acids and oils for food applications has been a big challenge. However, recent advances with transglutaminase (TGase) enzyme as an effective protein cross-linker could provide workable solutions for the encapsulation of omega-3 and omega-6 fatty acids without compromising their targeted release and their biological and physicochemical characteristics. The recent and available literature related to the microencapsulation techniques, physical and oxidative properties, and core retention and release mechanisms of TGase-crosslinked microcapsules entrapping edible oils were reviewed. The effects of factors involved in microencapsulation processes, on the efficiency and quality of the produced innovative microcapsules were also discussed and highlighted. A brief focus has been finally addressed to new insights and additional knowledge on micro- and nanoencapsulation of lipophilic food-grade ingredients by TGase-induced gelation. Two dominant microencapsulation methods for fish, vegetable, and essential oils by TGase-crosslinking are complex coacervation and emulsion-based spray drying. The developed spherical particles (<100 µm) with some wrinkles and smooth surfaces showed an excellent encapsulation efficiency and yield. A negligible release rate and a substantial retention level can result for different lipid-based cores covered by TGase-crosslinked proteins during the oral digestion and storage. A significant structural, thermal and oxidative stability for edible oils-loaded microcapsules in the presence of TGase can be also obtained.

Molecular, Physiological and Phenotypic Characterization of Paracoccus denitrificans ATCC 19367 Mutant Strain P-87 Producing Improved Coenzyme Q10.

Coenzyme Q10 (CoQ10) is a blockbuster nutraceutical molecule which is often used as an oral supplement in the supportive therapy for cardiovascular diseases, cancer and neurodegenerative diseases. It is commercially produced by fermentation process, hence constructing the high yielding CoQ10 producing strains is a pre-requisite for cost effective production. Paracoccus denitrificans ATCC 19367, a biochemically versatile organism was selected to carry out the studies on CoQ10 yield improvement. The wild type strain was subjected to iterative rounds of mutagenesis using gamma rays and NTG, followed by selection on various inhibitors like CoQ10 structural analogues and antibiotics. The screening of mutants were carried out using cane molasses based optimized medium with feeding strategies at shake flask level. In the course of study, the mutant P-87 having marked resistance to gentamicin showed 1.25-fold improvements in specific CoQ10 content which was highest among all tested mutant strains. P-87 was phenotypically differentiated from the wild type strain on the basis of carbohydrate assimilation and FAME profile. Molecular differentiation technique based on AFLP profile showed intra specific polymorphism between wild type strain and P-87. This study demonstrated the beneficial outcome of induced mutations leading to gentamicin resistance for improvement of CoQ10 production in P. denitrificans mutant strain P-87. To investigate the cause of gentamicin resistance, rpIF gene from P-87 and wild type was sequenced. No mutations were detected on the rpIF partial sequence of P-87; hence gentamicin resistance in P-87 could not be conferred with rpIF gene. However, detecting the mutations responsible for gentamicin resistance in P-87 and correlating its role in CoQ10 overproduction is essential. Although only 1.25-fold improvement in specific CoQ10 content was achieved through mutant P-87, this mutant showed very interesting characteristic, differentiating it from its wild type parent strain P. denitrificans ATCC 19367, which are presented in this paper.

Association rule mining of cellular responses induced by metal and metal oxide nanoparticles.

Relationships among fourteen different biological responses (including ten signaling pathway activities and four cytotoxicity effects) of murine macrophage (RAW264.7) and bronchial epithelial (BEAS-2B) cells exposed to six metal and metal oxide nanoparticles (NPs) were analyzed using both statistical and data mining approaches. Both the pathway activities and cytotoxicity effects were assessed using high-throughput screening (HTS) over an exposure period of up to 24 h and concentration range of 0.39-200 mg L(-1). HTS data were processed by outlier removal, normalization, and hit-identification (for significantly regulated cellular responses) to arrive at reliable multiparametric bioactivity profiles for the NPs. Association rule mining was then applied to the bioactivity profiles followed by a pruning process to remove redundant rules. The non-redundant association rules indicated that "significant regulation" of one or more cellular responses implies regulation of other (associated) cellular response types. Pairwise correlation analysis (via Pearson's χ(2) test) and self-organizing map clustering of the different cellular response types indicated consistency with the identified non-redundant association rules. Furthermore, in order to explore the potential use of association rules as a tool for data-driven hypothesis generation, specific pathway activity experiments were carried out for ZnO NPs. The experimental results confirmed the association rule identified for the p53 pathway and mitochondrial superoxide levels (via MitoSox reagent) and further revealed that blocking of the transcriptional activity of p53 lowered the MitoSox signal. The present approach of using association rule mining for data-driven hypothesis generation has important implications for streamlining multi-parameter HTS assays, improving the understanding of NP toxicity mechanisms, and selection of endpoints for the development of nanomaterial structure-activity relationships.

Differential effect of solar light in increasing the toxicity of silver and titanium dioxide nanoparticles to a fish cell line and zebrafish embryos.

The increasing use of silver (Ag) and titanium dioxide (TiO2) nanoparticles (NPs) in consumer products and their inevitable seepage into the environment prompted us to investigate their potential toxicity to a fish cell line (BF-2) and zebrafish embryos under dark and Simulated Solar Light (SSL) exposure conditions. Using high throughput screening (HTS) platforms, we showed that the oxidative stress-dependent cytotoxicity and embryonic toxicity of NPs were significantly increased upon exposure to SSL. While, the toxicity of TiO2 NPs under SSL exposure could be explained by hydroxyl radical generation, the enhanced toxicity of Ag NPs under SSL exposure was due to surface oxidation and physicochemical modification of Ag NPs and shedding of Ag+, leading to an increased bioavailability of silver. Our observations that solar light could induce physicochemical transformation of TiO2 and Ag NPs and enhance their toxic potential emphasizes the need for conducting future toxicity studies under environmentally relevant exposure conditions to guide decision making on the safe handling of NPs.

Morphological and Molecular Differentiation of Sporidiobolus johnsonii ATCC 20490 and Its Coenzyme Q10 Overproducing Mutant Strain UF16.

Coenzyme Q10 (CoQ10) is an industrially important molecule having nutraceutical and cosmeceutical applications. CoQ10 is mainly produced by microbial fermentation and the process demands the use of strains with high productivity and yields of CoQ10. During strain improvement program consisting of sequential induced mutagenesis, rational selection and screening process, a mutant strain UF16 was generated from Sporidiobolus johnsonii ATCC 20490 with 2.3-fold improvements in CoQ10 content. EMS and UV rays were used as mutagenic agents for generating UF16 and it was rationally selected based on atorvastatin resistance as well as survival at free radicals exposure. We investigated the genotypic and phenotypic changes in UF16 in order to differentiate it from wild type strain. Morphologically it was distinct due to reduced pigmentation of colony, reduced cell size and significant reduction in mycelial growth forms with abundance of yeast forms. At molecular level, UF16 was differentiated based on PCR fingerprinting method of RAPD as well as large and small-subunit rRNA gene sequences. Rapid molecular technique of RAPD analysis using six primers showed 34 % polymorphic fragments with mean genetic distance of 0.235. The partial sequences of rRNA-gene revealed few mutation sites on nucleotide base pairs. However, the mutations detected on rRNA gene of UF16 were less than 1 % of total base pairs and its sequence showed 99 % homology with the wild type strain. These mutations in UF16 could not be linked to phenotypic or genotypic changes on CoQ10 biosynthetic pathway that resulted in improved yield. Hence, investigating the mutations responsible for deregulation of CoQ10 pathway is essential to understand the cause of overproduction in UF16. Phylogenetic analysis based on RAPD bands and rRNA gene sequences coupled with morphological variations, exhibited the novelty of mutant UF16 having potential for improved CoQ10 production.

Emerging in vitro models for safety screening of high-volume production nanomaterials under environmentally relevant exposure conditions.

The rising production of nanomaterial-based consumer products has raised safety concerns. Testing these with animal and other direct models is neither ethically nor economically viable, nor quick enough. This review aims to discuss the strength of in vitro testing, including the use of 2D and 3D cultures, stem cells, and tissue constructs, etc., which would give fast and repeatable answers of a highly specific nature, while remaining relevant to in vivo outcomes. These results can then be combined and the overall toxicity predicted with relative accuracy. Such in vitro models can screen potentially toxic nanomaterials which, if required, can undergo further stringent studies in animals. The cyto- and phototoxicity of some high-volume production nanomaterials, using in vitro models, is also reviewed.

Size of TiO(2) nanoparticles influences their phototoxicity: an in vitro investigation.

To uncover the size influence of TiO(2) nanoparticles on their potential toxicity, the cytotoxicity of different-sized TiO(2) nanoparticles with and without photoactivation was tested. It was demonstrated that without photoactivation, TiO(2) nanoparticles were inert up to 100 µg/ml. On the contrary, with photoactivation, the toxicity of TiO(2) nanoparticles significantly increased, which correlated well with the specific surface area of the particles. Our results also suggest that the generation of hydroxyl radicals and reactive oxygen species (ROS)-mediated damage to the surface-adsorbed biomolecules could be the two major reasons for the cytotoxicity of TiO(2) nanoparticles after photoactivation. Higher ROS generation from smaller particles was detected under both biotic and abiotic conditions. Smaller particles could adsorb more proteins, which was confirmed by thermogravimetric analysis. To further investigate the influence of the generation of hydroxyl radicals and adsorption of protein, poly (ethylene-alt-maleic anhydride) (PEMA) and chitosan were used to coat TiO(2) nanoparticles. The results confirmed that surface coating of TiO(2) nanoparticles could reduce such toxicity after photoactivation, by hindering adsorption of biomolecules and generation of hydroxyl radical (·OH) during photoactivation.

Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles.

The aim of this study is to uncover the size influence of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles on their potential cytotoxicity. PLGA and TiO(2) nanoparticles of three different sizes were thoroughly characterized before in vitro cytotoxic tests which included viability, generation of reactive oxygen species (ROS), mitochondrial depolarization, integrity of plasma membrane, intracellular calcium influx and cytokine release. Size-dependent cytotoxic effect was observed in both RAW264.7 cells and BEAS-2B cells after cells were incubated with PLGA or TiO(2) nanoparticles for 24 h. Although PLGA nanoparticles did not trigger significantly lethal toxicity up to a concentration of 300 µg/ml, the TNF-α release after the stimulation of PLGA nanoparticles should not be ignored especially in clinical applications. Relatively more toxic TiO(2) nanoparticles triggered cell death, ROS generation, mitochondrial depolarization, plasma membrane damage, intracellular calcium concentration increase and size-dependent TNF-α release, especially at a concentration higher than 100 µg/ml. These cytotoxic effects could be due to the size-dependent interaction between nanoparticles and biomolecules, as smaller particles tend to adsorb more biomolecules. In summary, we demonstrated that the ability of protein adsorption could be an important paradigm to predict the in vitro cytotoxicity of nanoparticles, especially for low toxic nanomaterials such as PLGA and TiO(2) nanoparticles.

Characterization of size-differentiated airborne particulate matter collected from indoor environments of childcare facilities.

Inhalation of particulate matter (PM) present in indoor atmospheres has been associated with poor health and wellbeing of occupants. Here we report the characteristics of airborne PM collected from twenty-two air-conditioned childcare centres in Singapore. Airborne PM were collected using cascade impactors and characterized for morphology, elemental composition, endotoxin levels, ability to generate abiotic reactive oxygen species, and oxidative stress-dependent cytotoxicity in BEAS-2B cell lines. The mass concentrations of ultrafine particles (PM0.06-1) were more abundant than that of larger particles (PM1-4, PM4-20, and PM20-35 particles). PM20-35 and PM4-20 were irregularly shaped particles, PM1-4 particles had membranous flaky structures and PM0.06-1 particles were pseudo-spherical with the occasional presence of crystalline structures. Carbonaceous matter dominated PM20-35 particles, and the abundance of inorganic salts, iron and sulfur increased with decreasing PM size. Measured endotoxin levels were especially higher in PM4-20 particles. Compared to other particle size fractions, PM0.06-1 particles generated the highest ROS and were also the most potent in generating intracellular ROS in BEAS-2B cell lines. However, total mass concentrations, elemental compositions, abiotic responses, and PM collected from centres with split air-conditioning systems and no active outdoor air supply (SAC) were not statistically different compared with PM collected from centres with air conditioning with mechanical ventilation (ACMV). In conclusion, our study showed obvious distinctions in mass concentrations, morphology, elemental compositions, and cytotoxic potential of different sized particles collected from childcare centres, where the smallest particles (PM0.06-1) exhibited higher hazard potential.

Composite of Layered Double Hydroxide with Casein and Carboxymethylcellulose as a White Pigment for Food Application.

Titanium dioxide (TiO2) is commonly used in food, cosmetic, and pharmaceutical industries as a white pigment due to its extraordinary light scattering properties and high refractive index. However, as evidenced from recent reports, there are overriding concerns about the safety of nanoparticles of TiO2. As an alternative to TiO2, Mg-Al layered double hydroxide (LDH) and their composite containing casein and carboxymethyl cellulose (CMC) were synthesized using wet chemistry and compared with currently used materials (food grade TiO2 (E171), rice starch, and silicon dioxide (E551)) for its potential application as a white pigment. These particles were characterized for their size and shape (Transmission Electron Microscopy), crystallographic structure (X-Ray Diffraction), agglomeration behavior and surface charge (Dynamic Light Scattering), surface chemistry (Fourier Transform Infrared Spectroscopy), transmittance (UV-VIS spectroscopy), masking power, and cytotoxicity. Our results showed the formation of typical layered double hydroxide with flower-like morphology which was restructured into pseudo-spheres after casein intercalation. Transmittance measurement showed that LDH composites had better performance than pristine LDH, and the aqueous suspension was heat and pH resistant. While its masking power was not on a par with E171, the composite of LDH was superior to current alternatives such as rice starch and E551. Sustainability score obtained by MATLAB® based comparison for price, safety, and performance showed that LDH composite was better than any of the compared materials, highlighting its potential as a white pigment for applications in food.

Inorganic food additive nanomaterials alter the allergenicity of milk proteins.

While inorganic nanomaterials are copiously incorporated in food products, their impact on the allergenicity food proteins is largely unknown. This study analyzed the effect of widely used food additive nanomaterials (silica and titania) on the antigenicity and allergenicity of milk proteins (ß-lactoglobulin and casein) and skimmed milk. Changes in the antigenicity of milk proteins in the presence of dietary nanomaterials were identified using an indirect-ELISA assay, while the change in allergenicity was studied using mast cell (LAD2) sensitized using allergic human sera. Results showed an enhancement in the allergenicity of milk proteins/skimmed milk interacted with particles (both silica and titania). Similarly, mast cell degranulation (a proxy for allergenicity) was higher when exposed to particle interacted skim milk where nanomaterials of titania showed the highest effect, and this tendency was retained even after subjecting to simulated gut digestion. Particles induced alterations in the structure of milk proteins, as evidenced by our studies, are reasoned to expose epitopes that increase allergenicity of milk proteins.

Light activation of gold nanorods but not gold nanospheres enhance antibacterial effect through photodynamic and photothermal mechanisms.

Plasmonic nanomaterials of gold and silver have been reported to have antibacterial effect. In this study, three gold nanomaterials (NMs) of different aspect rations (Gold nanospheres (AuNSs, aspect ratio 1), and two gold nanorods (AuNRs636, aspect ratio 2.79; AuNRs772, aspect ratio 3.42)) and silver nanoparticles (AgNPs) were synthesized, characterized and the effect of incandescent light on their antibacterial properties were examined. Bacterial inactivation during photoinactivation of nanomaterials and antibacterial mechanisms (biotic ROS, membrane potential, membrane damage) were investigated using Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Salmonella enterica serovar Typhimurium, and methicillin-resistant S. aureus. The results indicated that AuNSs had no antibacterial activity in the tested concentration (0.49-250 µg/mL), while AuNR636 and AuNRs772 showed significant bactericidal effect on all tested bacteria. Notably, AuNRs636 presented higher antibacterial effect than AuNRs772, which could result from higher surface reactivity of AuNRs636 owing to higher dangling bonds. Further studies showed that AuNRs but not AuNSs generated hydroxyl radicals (·OH) (photodynamic effect) and photothermal effect when exposed to incandescent light. The combined photodynamic and photothermal effect resulted in bacterial inactivation through cell membrane damage, lowering of cell membrane potential and DNA degradation. In summary, this investigation showed that Au NRs but not Au NSs exhibit photodynamic and photothermal effects suggesting the potential of fabricating material surfaces with Au NRs for photoactivated bacterial inactivation.

Hazard profiling of a combinatorial library of zinc oxide nanoparticles: Ameliorating light and dark toxicity through surface passivation.

Zinc oxide (ZnO) is one of the high-volume production nanoparticles (NPs) currently used in a wide range of consumer and industrial goods. The inevitable seepage into environmental matrices and the photoactive nature of ZnO NPs warrants hazard profiling under environmentally related conditions. In this paper, the influence of simulated solar light (SSL) on dissolution behaviour and phototoxicity of ZnO NPs was studied using a combinatorial library of ZnO NPs with different sizes, surface coatings, dopant chemistry, and aspect ratios in a fish cell line (BF2) and zebrafish embryos. Generally, the cytotoxicity and embryo mortality increased when exposed concomitantly to SSL and ZnO NPs. The increase in toxic potential of ZnO NPs during SSL exposure concurred with release of Zn ions and ROS generation. Surface modification of NPs with poly(methacrylic acid) (PMAA), silica or serum coating decreased toxicity and ZnO with serum coating was the only NP that had no significant effect on any of the cytotoxicity parameters when tested under both dark and SSL conditions. Results from our study show that exposure to light could increase the toxic potential of ZnO NPs to environmental lifeforms and mitigation of ZnO NP toxicity is possible through modifying the surface chemistry.

Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs.

The emergence of multidrug-resistant (MDR) bacterial pathogens in farm animals and their zoonotic spread is a concern to both animal agriculture and public health. Apart from antimicrobial resistance (AMR), bacterial pathogens from the genera of Salmonella and Staphylococcus take refuge inside host cells, thereby demanding intervention strategies that can eliminate intracellular MDR pathogens. In this study, seven clinical isolates of Salmonella and Staphylococcus from swine farms were characterized for antibiotic (n = 24) resistance, resistance mechanisms, and virulence characteristics. All isolates showed resistance to one or more antibiotics and S. enterica ser. Typhimurium isolate had the highest resistance to the panel of antibiotics tested. Major resistance mechanisms identified were efflux pump and beta-lactamase enzyme activities. Staphylococcus isolates showed complete hemolysis and strong biofilm formation, while Salmonella isolates caused partial hemolysis, but showed no or weak biofilm formation. MDR isolates of S. aureus M12 and S. enterica ser. Typhimurium bacteria were subsequently tested against combinations of antibiotics and potentiating adjuvants for improved antibacterial efficacy using a checkerboard assay, and their fractional inhibitory concentration index (FICI) was calculated. A combination of chitosan and silica nanoparticles containing tetracycline (TET) and efflux pump inhibitor chlorpromazine (CPZ), respectively, was characterized for physicochemical properties and effectiveness against MDR Salmonella enterica ser. Typhimurium isolate. This combination of nano-encapsulated drugs improved the antibacterial efficacy by inhibiting AMR mechanisms (efflux activity, beta-lactamase enzyme activity, and hydrogen sulfide (H2S) production) and reducing intracellular pathogen load by 83.02 ± 14.35%. In conclusion, this study sheds light on the promising applicability of nanoparticle-enabled combination therapy to combat multidrug-resistant pathogens encountered in animal agriculture.