Can We Exploit β-Lactamases Intrinsic Dynamics for Designing More Effective Inhibitors?

β-lactamases (BLs) represent the most frequent cause of antimicrobial resistance in Gram-negative bacteria. Despite the continuous efforts in the development of BL inhibitors (BLIs), new BLs able to hydrolyze the last developed antibiotics rapidly emerge. Moreover, the insurgence rate of effective mutations is far higher than the release of BLIs able to counteract them. This results in a shortage of antibiotics that is menacing the effective treating of infectious diseases. The situation is made even worse by the co-expression in bacteria of BLs with different mechanisms and hydrolysis spectra, and by the lack of inhibitors able to hit them all. Differently from other targets, BL flexibility has not been deeply exploited for drug design, possibly because of the small protein size, for their apparent rigidity and their high fold conservation. In this mini-review, we discuss the evidence for BL binding site dynamics being crucial for catalytic efficiency, mutation effect, and for the design of new inhibitors. Then, we report on identified allosteric sites in BLs and on possible allosteric inhibitors, as a strategy to overcome the frequent occurrence of mutations in BLs and the difficulty of competing efficaciously with substrates. Nevertheless, allosteric inhibitors could work synergistically with traditional inhibitors, increasing the chances of restoring bacterial susceptibility towards available antibiotics

LED lighting systems for horticulture: Business growth and global distribution

In recent years, research on light emitting diodes (LEDs) has highlighted their great potential as a lighting system for plant growth, development and metabolism control. The suitability of LED devices for plant cultivation has turned the technology into a main component in controlled or closed plant-growing environments, experiencing an extremely fast development of horticulture LED metrics. In this context, the present study aims to provide an insight into the current global horticulture LED industry and the present features and potentialities for LEDs' applications. An updated review of this industry has been integrated through a database compilation of 301 manufacturers and 1473 LED lighting systems for plant growth. The research identifies Europe (40%) and North America (29%) as the main regions for production. Additionally, the current LED luminaires' lifespans show 10 and 30% losses of light output after 45,000 and 60,000 working hours on average, respectively, while the vast majority of worldwide LED lighting systems present efficacy values ranging from 2 to 3 μmol J-1 (70%). Thus, an update on the status of the horticultural LED sector, LEDs' applications and metrics, and the intense innovation are described and discussed

Eco-efficiency assessment and food security potential of home gardening: a case study in Padua, Italy

In the expanding urban agriculture phenomenon in Europe, home gardens are a traditional form that have kept agriculture within cities, even becoming crucial in certain historical periods (e.g., war periods). However, horticultural practices in home gardens can also have negative consequences. The goal of this paper is to assess the eco-efficiency of home gardens as a type of urban agriculture. To do so, a case study in Padua (Italy) was evaluated following life cycle assessment and life cycle costing methods. A home garden of 30.6 m(2) and 21 crop cycles were evaluated. The functional unit of the assessment was 1 kg of harvested fresh vegetable at the consumption point, and the ReCiPe method was employed for impact assessment. Environmental assessment indicated that organic fertilization, use of tap water, mineral fertilization and pesticides were the most contributing elements of the entire life cycle. Furthermore, the relevance of garden design and crop selection was a determinant in the eco-efficiency results. The assessed home garden could satisfy the food requirements of between 1 and 2 members of the household. Crop management and design recommendations are provided to improve eco-efficiency and food security potential of home gardens

Supplemental LED Lighting Improves Fruit Growth and Yield of Tomato Grown under the Sub-Optimal Lighting Condition of a Building Integrated Rooftop Greenhouse (i-RTG)

The metabolism of a building can be connected to a rooftop greenhouse, exchanging energy, water and CO2 flows, therefore reducing emissions and recycling cultivation inputs. However, integrating a rooftop greenhouse onto a building requires the application of stringent safety codes (e.g., fire, seismic codes), to strengthen and secure the structure with safety elements such as thick steel pillars or fireproof covering materials. These elements can shade the vegetation or reduce solar radiation entering the rooftop greenhouse. Nevertheless, application of additional LED light can help to overcome this constraint. The present study evaluated supplemental LED light application in an integrated rooftop greenhouse (i-RTG) at the ICTA-UAB research institute, located in Barcelona (Spain), for tomato cultivation (Solanum lycopersicum cv. Siranzo). The experiment explored the effects of three LED lighting treatments and a control cultivated under natural light only (CK). Applied treatments, added to natural sunlight, were: red and blue (RB), red and blue + far-red (FR) for the whole day, and red and blue + far-red at the end-of-day (EOD), each for 16 h d(-1) (8 a.m.-12 a.m.) with an intensity of 170 mu mol m(-2) s(-1). The results indicate that LED light increased the overall yield by 17% compared with CK plants. In particular, CK tomatoes were 9.3% lighter and 7.2% fewer as compared with tomatoes grown under LED treatments. Fruit ripening was also affected, with an increase of 35% red proximal fruit in LED-treated plants. In conclusion, LED light seems to positively affect the development and growth of tomatoes in building integrated agriculture in the Mediterranean area

Natural products as novel scaffolds for the design of glycogen synthase kinase 3β inhibitors

Introduction: The different and relevant roles of GSK-3 are of critical importance since they deal with development, metabolic homeostasis, cell polarity and fate, neuronal growth and differentiation as well as modulation of apoptotic potential. Given their involvement with different diseases, many investigations have been undertaken with the aim of discovering new and promising inhibitors for this target. In this context, atural products represent an invaluable source of active molecules. Areas covered: In order to overcome issues such as poor pharmacokinetic properties or efficacy, frequently associated with natural compounds, different GSK-3β inhibitors belonging to alkaloid or flavonoid classes have been subjected to structural modifications in order to obtain more potent and safer compounds. Herein, the authors report the results obtained from studies where natural compounds have been used as hits with the aim of providing new kinase inhibitors endowed with a better inhibitory profile. Expert opinion: Structurally modification of natural scaffolds is a proven approach taking advantage of their pharmacological characteristics. Indeed, whatever the strategy adopted is and, despite the limitations associated with the structural complexity of natural products, the authors recommend the use of natural scaffolds as a promising strategy for the discovery of novel and potent GSK-3β inhibitors

Iron metabolism at the interface between host and pathogen: From nutritional immunity to antibacterial development

Nutritional immunity is a form of innate immunity widespread in both vertebrates and invertebrates. The term refers to a rich repertoire of mechanisms set up by the host to inhibit bacterial proliferation by sequestering trace minerals (mainly iron, but also zinc and manganese). This strategy, selected by evolution, represents an effective front-line defense against pathogens and has thus inspired the exploitation of iron restriction in the development of innovative antimicrobials or enhancers of antimicrobial therapy. This review focuses on the mechanisms of nutritional immunity, the strategies adopted by opportunistic human pathogen Staphylococcus aureus to circumvent it, and the impact of deletion mutants on the fitness, infectivity, and persistence inside the host. This information finally converges in an overview of the current development of inhibitors targeting the different stages of iron uptake, an as-yet unexploited target in the field of antistaphylococcal drug discovery

Iron metabolism at the interface between host and pathogen: From nutritional immunity to antibacterial development

Nutritional immunity is a form of innate immunity widespread in both vertebrates and invertebrates. The term refers to a rich repertoire of mechanisms set up by the host to inhibit bacterial proliferation by sequestering trace minerals (mainly iron, but also zinc and manganese). This strategy, selected by evolution, represents an effective front-line defense against pathogens and has thus inspired the exploitation of iron restriction in the development of innovative antimicrobials or enhancers of antimicrobial therapy. This review focuses on the mechanisms of nutritional immunity, the strategies adopted by opportunistic human pathogen Staphylococcus aureus to circumvent it, and the impact of deletion mutants on the fitness, infectivity, and persistence inside the host. This information finally converges in an overview of the current development of inhibitors targeting the different stages of iron uptake, an as-yet unexploited target in the field of antistaphylococcal drug discovery

Cryo-EM undiscloses structural and mechanistic details on iron hijacking by Staphylococcus aureus: An insight into the interaction of IsdB hemophore with human hemoglobin

Iron is an essential nutrient for almost all organisms. In the human body, it is primarily bound to the heme cofactor of hemoglobin (Hb), myoglobin and other heme-binding proteins. During infection, Staphylococcus aureus exploits Hb heme pool as its favored iron source, capturing and internalizing it by cell wall hemophores. The first step is performed by IsdB, which intercepts free Hb and extracts heme. IsdB, a proven virulence factor, is an attractive putative target for antimicrobials development but its mechanism of action needs to be further detailed. To this aim, we used cryo-EM single-particle analysis to study IsdB:Hb complex formation and heme extraction. The key complexes before and after heme extraction were solved at 2.9 ˚ Aand5.8˚ A resolution using carboxyHb, resistant to heme removal, and oxidized Hb, the physiologic IsdB substrate. IsdB first binds to Hb β-chains, enhancing Hb dimerization to favor a second IsdB molecule binding to α-chains before extraction. These results greatly improve our current knowledge of IsdB structural and functional dynamics, thus promoting future studies on new potential antimicrobials aimed at impairing S. aureus iron acquisition

Potential application of pre-harvest LED interlighting to improve tomato quality and storability

Growing conditions and agronomical inputs play a key role in determining fruit qualitative and nutraceutical traits at harvest and post-harvest. The hereby presented research investigated the effects of pre-harvest supplemental LED interlighting on post-harvest quality of hydroponically grown tomatoes (Solanum lycopersicum “Siranzo”). Three LED treatments, applied for 16 h d-1 (h 8.00–00.00), were added to natural sunlight and consisted of Red and Blue (RB), Red and Blue + Far-Red (FR), and Red and Blue + Far-Red at the end-of-day for 30 min (EOD), with an intensity of 180 µmol m-2 s-1 for Red and Blue, plus 44 µmol m-2 s-1 for Far-Red. A control treatment (CK), where plants were grown only with sunlight, was also considered. Fruits at red stage were selected and placed in a storage room at 13 °C in darkness. Fruit quality assessment was performed at harvest time and after one week of storage. RB and FR increased fruit firmness compared to CK, opening possible benefits toward reducing fruit losses during post-harvest handling. RB treated fruits also maintained a higher content of lycopene and β-carotene after the first week of storage. The study demonstrates that supplementary LED interlighting during greenhouse tomato cultivation may enhance storability and help preserve fruit nutritional properties during post-harvest