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Molecular communication between macromolecules dictates extracellular matrix (ECM) dynamics during pathogen recognition and disease development. Extensive research has shed light on how plant immune components are activated, regulated and function in response to pathogen attack. However, two key questions remain largely unresolved: (i) how does ECM dynamics govern susceptibility and disease resistance, (ii) what are the components that underpin these phenomena? Rice blast, caused by Magnaporthe oryzae adversely affects rice productivity. To understand ECM regulated genotype-phenotype plasticity in blast disease, we temporally profiled two contrasting rice genotypes in disease and immune state. Morpho-histological, biochemical and electron microscopy analyses revealed that increased necrotic lesions accompanied by electrolyte leakage governs disease state. Wall carbohydrate quantification showed changes in pectin level was more significant in blast susceptible compared to blast resistant cultivar. Temporally resolved quantitative disease- and immune-responsive ECM proteomes identified 308 and 334 proteins, respectively involved in wall remodelling and integrity, signalling and disease/immune response. Pairwise comparisons between time and treatment, messenger ribonucleic acid expression, diseasome and immunome networks revealed novel blast-related functional modules. Data demonstrated accumulation of α-galactosidase and phosphatase were associated with disease state, while reactive oxygen species, induction of Lysin motif proteins, CAZymes and extracellular Ca-receptor protein govern immune state.
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The aim of the present study was nanoencapsulation of thymol to improve its poor water solubility and preservation of encapsulated thymol against environmental conditions. Another goal of the current investigation was to assess the antibacterial activity of thymol nanoemulsion as a sustainable biopesticide to control the bacterial blight of cluster bean. An oil-in-water (o/w) nanoemulsion containing thymol was prepared by a high-energy emulsification method using gum acacia and soya lecithin as natural emulsifiers/surfactants. The characterization of thymol nanoemulsion was carried out using dynamic light scattering (DLS), transmission electron microscope (TEM) and Fourier transform infrared spectroscopy (FTIR). A mean particle size of about 83.38 nm was recorded within 10 min of sonication. The stability analysis of optimized nanoemulsion showed kinetic stability up to two months of storage at room temperature. The thymol nanoemulsion was found to be spherical with a size ranging from 80-200 nm in diameter using transmission electron microscopy. Fourier transform infrared spectroscopy was used to study the molecular interaction between emulsifier/surfactant and thymol. The antibacterial studies of thymol nanoemulsion (0.01-0.06%, v/v) by growth inhibition analysis showed a potential antibacterial effect against Xanthomonas axonopodis pv. cyamopsidis (18-0.1 log CFU/ml). Further, in field experiments, foliar spray of the different concentration of thymol nanoemulsion (0.01-0.06%, v/v) significantly increased the percent efficiency of disease control (25.06-94.48%) and reduced the disease intensity (67.33-4.25%) of bacterial blight in cluster bean.
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Seed longevity is a measure of the viability of seeds during long-term storage and is crucial for germplasm conservation and crop improvement programs. Also, longevity is an important trait for ensuring food and nutritional security. Thus, a better understanding of various factors regulating seed longevity is requisite to improve this trait and to minimize the genetic drift during the regeneration of germplasm. In particular, seed deterioration of cereal crops during storage adversely affects agricultural productivity and food security. The irreversible process of seed deterioration involves a complex interplay between different genes and regulatory pathways leading to: loss of DNA integrity, membrane damage, inactivation of storage enzymes and mitochondrial dysfunction. Identifying the genetic determinants of seed longevity and manipulating them using biotechnological tools hold the key to ensuring prolonged seed storage. Genetics and genomics approaches had identified several genomic regions regulating the longevity trait in major cereals such as: rice, wheat, maize and barley. However, very few studies are available in other Poaceae members, including millets. Deploying omics tools, including genomics, proteomics, metabolomics, and phenomics, and integrating the datasets will pinpoint the precise molecular determinants affecting the survivability of seeds. Given this, the present review enumerates the genetic factors regulating longevity and demonstrates the importance of integrated omics strategies to dissect the molecular machinery underlying seed deterioration. Further, the review provides a roadmap for deploying biotechnological approaches to manipulate the genes and genomic regions to develop improved cultivars with prolonged storage potential.
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Grão Comestível , Longevidade , Grão Comestível/genética , Longevidade/genética , Sementes/genética , Sementes/metabolismo , Produtos Agrícolas/genética , ProteômicaRESUMO
Kodo millet (Paspalum scrobiculatum L.) is a small millet species known for its excellent nutritional and climate-resilient traits. To understand the genes and pathways underlying dehydration stress tolerance of kodo millet, the transcriptome of cultivar 'CO3' subjected to dehydration stress (0 h, 3 h, and 6 h) was sequenced. The study generated 239.1 million clean reads that identified 9201, 9814, and 2346 differentially expressed genes (DEGs) in 0 h vs. 3 h, 0 h vs. 6 h, and 3 h vs. 6 h libraries, respectively. The DEGs were found to be associated with vital molecular pathways, including hormone metabolism and signaling, antioxidant scavenging, photosynthesis, and cellular metabolism, and were validated using qRT-PCR. Also, a higher abundance of uncharacterized genes expressed during stress warrants further studies to characterize this class of genes to understand their role in dehydration stress response. Altogether, the study provides insights into the transcriptomic response of kodo millet during dehydration stress.
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Paspalum , Desidratação/genética , Perfilação da Expressão Gênica , Transcriptoma , Antioxidantes , Regulação da Expressão Gênica de PlantasRESUMO
Soil salinity is one of the major threats that pose challenges to global cereal productivity and food security. Cereals have evolved sophisticated mechanisms to circumvent stress at morpho-physiological, biochemical, and molecular levels. Salt stress cues are perceived by the roots, which trigger the underlying signaling pathways that involve phytohormones. Each phytohormone triggers a specific signaling pathway integrated in a complex manner to produce antagonistic, synergistic, and additive responses. Phytohormones induce salt-responsive signaling pathways to modulate various physiological and anatomical mechanisms, including cell wall repair, apoplastic pH regulation, ion homeostasis, root hair formation, chlorophyll content, and leaf morphology. Exogenous applications of phytohormones moderate the adverse effects of salinity and improve growth. Understanding the complex hormonal crosstalk in cereals under salt stress will advance the knowledge about cooperation or antagonistic mechanisms among hormones and their role in developing salt-tolerant cereals to enhance the productivity of saline agricultural land. In this context, the present review focuses on the mechanisms of hormonal crosstalk that mediate the salt stress response and adaptation in graminaceous crops.
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Salinidade , Tolerância ao Sal , Produtos Agrícolas , Reguladores de Crescimento de Plantas , Estresse Salino , Estresse FisiológicoRESUMO
Modulation of plant immune system by extrinsic/intrinsic factors and host-specific determinants fine-tunes cellular components involving multiple organelles, particularly nucleus to mount resistance against pathogen attack. Rice blast, caused by hemibiotrophic fungus Magnaporthe oryzae, is one of the most devastating diseases that adversely affect rice productivity. However, the role of nuclear proteins and their regulation in response to M. oryzae remains unknown. Here, the nucleus-associated immune pathways in blast-resistant rice genotype are elucidated. Temporal analysis of nuclear proteome is carried out using 2-DE coupled MS/MS analysis. A total of 140 immune responsive proteins are identified associated with nuclear reorganization, cell division, energy production/deprivation, signaling, and gene regulation. The proteome data are interrogated using correlation network analysis that identified significant functional modules pointing toward immune-related coinciding processes through a common mechanism of remodeling and homeostasis. Novel clues regarding blast resistance include nucleus-associated redox homeostasis and glycolytic enzyme-mediated chromatin organization which manipulates cell division and immunity. Taken together, the study herein provides evidence that the coordination of nuclear function and reprogramming of host translational machinery regulate resistance mechanism against blast disease.
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Magnaporthe/imunologia , Oryza/imunologia , Doenças das Plantas/imunologia , Proteínas de Plantas/imunologia , Resistência à Doença , Interações Hospedeiro-Patógeno , Magnaporthe/fisiologia , Oryza/microbiologia , Doenças das Plantas/microbiologia , Imunidade Vegetal , Transdução de Sinais , Espectrometria de Massas em TandemRESUMO
Alzheimer's disease (AD) is the sixth leading cause of death in the United States where it is estimated that one in three seniors dies with AD or another dementia. Are modern lifestyle habits a contributing factor? Increased carbohydrate (sugar) consumption, stress and disruption of sleep patterns are quickly becoming the norm rather than the exception. Interestingly, seven months on a non-invasive high sucrose diet (20% sucrose in drinking water) has been shown to induce behavioral, metabolic and pathological changes consistent with AD in wild-type mice. As chronic stress and depression are associated with loss of locus coeruleus (LC) noradrenergic neurons and projections (source of anti-inflammatory and trophic factor control), we assessed the ability for a selective LC neurotoxin (DSP4) to accelerate and aggravate a high-sucrose mediated AD-related phenotype in wild-type mice. Male C57/Bl6 mice were divided into four groups: 1) saline injected, 2) DSP4 injected, 3) high sucrose drinking water (20%) or 4) DSP4 injected and high sucrose drinking water. We demonstrate that high sucrose consumption and DSP4 treatment promote an early-stage AD-related phenotype after only 3-4 months, as evidenced by elevated fecal corticosterone, increased despair, spatial memory deficits, increased AChE activity, elevated NO production, decreased pGSK3ß and increased pTau. Combined treatment appears to accelerate and aggravate pathological processes consistent with Alzheimer disease and dementia. Developing a simple model in wild-type mice will highlight environmental and lifestyle factors that need to be addressed to slow, prevent or even reverse the rising trend in dementia patient numbers and cost.
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Doença de Alzheimer/patologia , Comportamento Animal/efeitos dos fármacos , Benzilaminas/farmacologia , Encéfalo/efeitos dos fármacos , Açúcares da Dieta/administração & dosagem , Neurotoxinas/farmacologia , Sacarose/administração & dosagem , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Dieta , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos , Atividade Motora/efeitos dos fármacos , Fosforilação , Proteínas tau/metabolismoRESUMO
The discovery of arrestin-mediated biased signalling mechanisms for mammalian G-protein coupled receptors (GPCRs) has revolutionized the field over the last decade. Now, with the recent demonstration of a role for α-arrestins in internalization of the yeast pheromone GPCR, Ste2p, the possibility of arrestin-mediated alternate GPCR functionalities in yeast also follows. Here, the effects of knockout and complementation of yeast α-arrestin expression during mating are reported. Although minor effects on classical pheromone-related signalling are noted for a few arrestins, much stronger effects were observed downstream of cell cycle arrest, in particular linking Ldb19 (Art1) to mediation of zygote formation. Subsequent phenotypic observations linked this activity to more pronounced projection formation in an Art1 complemented noncuple α-arrestin knockout line, compared to the knockout-line alone, or either of the Art3 or Art6 complemented lines. Together with the observation of ligand-stimulated localization of Art-GFP to the mating projection, a possible role for this arrestin-like protein in projection formation is supported. While leaving the full mechanism of alternate Art1 functionality to be elucidated, together these findings implicate Art1 in selective regulation of mating events downstream of receptor internalization and cell cycle arrest, leading to schmoo, and ultimately zygote formation.
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Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Genes Fúngicos Tipo Acasalamento , Ligantes , Fosforilação , Saccharomyces cerevisiae/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: The study of carvacrol plant antibacterial components has recently become a hot topic in modern farming. Carvacrol industrial applications are restricted by their physicochemical instability and partial solubility in water. In the present study, an ultrasonic emulsification method was used to prepare a carvacrol nanoemulsion (CAR-NE) employing nonionic surfactants. The CAR-NE was characterized using a dynamic light scattering (DLS) instrument and transmission electron microscopy (TEM). The goal of this work was nanoencapsulation of carvacrol to improve its aqueous solubility and preservation of the encapsulated compound against climatic conditions. Another aim of the present study was the evaluation of the growth-promoting effects and antibacterial potential of CAR-NE against bacterial leaf blight of cluster bean. RESULTS: CAR-NE showed a hydrodynamic diameter, ZP and PDI index of 43.88 ± 4.30 nm, -47.8 ± 0.23 mV and 0.246 ± 0.04, respectively. The spherical shape morphology of CAR-NE was confirmed by TEM imaging. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of the CAR-NE were 20 and 160 µL mL-1 (respectively) against Xanthomonas axonopodis pv. cyamopsidis. Additionally, the antibacterial potential of CAR-NE was evaluated for controlling bacterial blight of cluster bean in fields. The disease severity in the negative control plants (water) was 84%, but that in the CAR-NE 160 (µL mL-1 ) was remarkably low at 14%, nearly the same as the positive control (streptomycin sulfate). CONCLUSION: The shelf-life of CAR-NE was 2 months at room temperature without any appreciable changes in hydrodynamic diameter and zeta potential. Consequently, plants treated with CAR-NE 160 showed substantial improvement in plant growth. © 2023 Society of Chemical Industry.
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Antibacterianos , Agentes de Controle Biológico , Cimenos , Antibacterianos/farmacologia , ÁguaRESUMO
Molecular basis of rice aroma formation is sparsely known and developmental programs driving biochemical pathways towards aroma is in infancy. Here, discovery and targeted proteo-metabolome of non-aromatic and aromatic rice seeds across developmental stages identified a total of 442 aroma-responsive proteins (ARPs) and 824 aroma-responsive metabolites (ARMs) involved in metabolism, calcium and G-protein signaling. Biochemical examination revealed ARM/Ps were linked to 2-acetylpyrrolidine, γ-aminobutyrate, anthocyanin, tannins, flavonoids and related enzymes. Pairwise correlation and clustering showed positive correlation among ARM/Ps. Consistent with aroma-related QTLs, ARPs were mapped on chromosomes 3,4,5,8 and were mainly compartmentalized in cytoplasm and mitochondria. ARM/P-correlation network identified associations related to metabolism and signaling. Multiple reaction monitoring (MRM) confirmed role of catechins, quinic acid and quercetin in aroma formation. Pathway enrichment, multivariate analysis and qRT-PCR validated that calcium and G-protein signaling, aromatic/branched-chain aminoacid, 2-acetylpyrrolidine, oxylipin, melvonate and prenylpyrophosphate pathways, indole, phenylacetate, flavonoid, cinnamoic ester govern aroma formation in rice.
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Extracellular matrix (ECM) plays central roles in cell architecture, innate defense and cell wall integrity (CWI) signaling. During transition to multicellularity, modular domain structures of ECM proteins and proteoforms have evolved due to continuous adaptation across taxonomic clades under different ecological niche. Although this incredible diversity has to some extent been investigated at protein level, extracellular phosphorylation events and molecular evolution of ECM proteoform families remains unexplored. We developed matrisome proteoform atlas in a grain legume, chickpea and performed meta-analyses of 74 plant matrisomes. MS/MS analysis identified 1,424 proteins and 315 phosphoproteins involved in diverse functions. Cross-species ECM protein network identified proteoforms associated with CWI maintenance system. Phylogenetic characterization of eighteen matrix protein families highlighted the role of taxon-specific paralogs and orthologs. Novel information was acquired on gene expansion and loss, co-divergence, sub functionalization and neofunctionalization during evolution. Modular networks of matrix protein families and hub proteins showed higher diversity across taxonomic clades than among organs. Furthermore, protein families differ in nonsynonymous to synonymous substitution rates. Our study pointed towards the matrix proteoform functionality, sequence divergence variation, interactions between wall remodelers and molecular evolution using a phylogenetic framework. This is the first report on comprehensive matrisome proteoform network illustrating presence of CWI signaling proteins in land plants.
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Genetic diversity and relationships within and among members of the primary gene pool of chickpea, including 38 accessions of Cicer arietinum, six of C. reticulatum,, and four of C. echinospermum, were investigated using 31 ISSR markers. The study revealed moderate diversity, detecting 141 fragments, of which 79 (56%) were polymorphic. Averages were 0.125 for polymorphic information content, 0.350 for marker index, and 0.715 for resolving power. The UPGMA dendrogram and the principal coordinate analysis revealed a clear differentiation between wild and cultivated accessions. The clustering pattern did not strictly follow the grouping of accessions by geographic origin but was in good agreement with the pedigree data and the seed type. The study demonstrates that ISSRs provide promising marker tools in revealing genetic diversity and relationships in chickpea and can contribute to efficient identification, conservation, and utilization of germplasm for plant improvement through conventional as well as molecular breeding approaches.
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Cicer/genética , Genes de Plantas , Marcadores Genéticos , Variação Genética , Repetições de Microssatélites/genética , Genoma de Planta/genéticaRESUMO
Agriculture is facing the challenge of feeding the ever-growing population that is projected to reach ten billion by 2050. While improving crop yield and productivity can address this challenge, the increasing effects of global warming and climate change seriously threaten agricultural productivity. Thus, genomics and genome modification technologies are crucial to improving climate-resilient traits to enable sustained yield and productivity; however, significant research focuses on staple crops such as rice, wheat, and maize. Crops that are naturally climate-resilient and nutritionally superior to staple cereals, such as small millets, remain neglected and underutilized by mainstream research. The ability of small millets to grow in marginal regions having limited irrigation and poor soil fertility makes these crops a better choice for cultivation in arid and semi-arid areas. Hence, mainstreaming small millets for cultivation and using omics technologies to dissect the climate-resilient traits to identify the molecular determinants underlying these traits are imperative for addressing food and nutritional security. In this context, the review discusses the genomics and genome modification approaches for dissecting key traits in small millets and their application for improving these traits in cultivated germplasm. The review also discusses biofortification for nutritional security and machine-learning approaches for trait improvement in small millets. Altogether, the review provides a roadmap for the effective use of next-generation approaches for trait improvement in small millets. This will lead to the development of improved varieties for addressing multiple insecurities prevailing in the present climate change scenario.
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The immune system in the upper reproductive tract (URT) protects against sexually transmitted pathogens, while at the same time providing immune tolerance responses against allogenic sperm and the developing fetus. The uterine environment is also responsive to hormonal variations during the estrus cycle, although the most likely timing of exposure to pathogens is during estrus and breeding when the cervix is semi-permissive. The goal for intrauterine immunization would be to induce local or systemic immunity and/or to promote colostral/lactogenic immunity that will passively protect suckling offspring. The developing fetus is not the vaccine target. This minireview article focuses on the immune response induced in the pig uterus (uterine body and uterine horns) with some comparative references to other livestock species, mice, and humans.
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Sêmen , Útero , Feminino , Masculino , Humanos , Camundongos , Animais , Suínos , Mucosa , Imunidade , Desenvolvimento de VacinasRESUMO
Delayed release of vaccine coupled with a soluble vaccine acts as a primer and a booster with only a single administration, which would be very beneficial to livestock producers. We developed a subdermal pellet consisting of solid-phase pure stearic acid (SA) or palmitic acid (PA) that was used to encapsulate a small volume liquid vaccine consisting of fluorescently labeled *Ovalbumin (Cy5-*OVA) formulated with Emulsigen-D +/- Poly I:C (EMP) adjuvants. Mice were also immunized via the subcutaneous route with Cy5-*OVA-EMP (soluble liquid). The vaccine leached out of the pellet with very little dissolution of the fat itself resulting in the sustained subdermal delivery of antigens and adjuvants. Cy5-*OVA was still visible 60 days post administration in mice immunized with stearic acid-coated or palmitic acid-coated pellets. In these mice, persistently high IgG1 and IgG2a antibody titres were detected as well as significant IFNγ production at least 60 days post-injection. These responses were significantly higher than those observed after a single subcutaneous injection of the vaccine. A repeat trial with the pellets alone +/- the soluble vaccine showed comparable immune responses after surgical implantation of the pellet, suggesting that pellet alone may be sufficient. The PA-coated vaccines led to dermal inflammation in the mice that would limit usefulness of this vehicle, but this was largely absent when SA was used to coat the pellets. These data suggest that the SA-coated adjuvanted vaccine prolonged the release of the vaccine and triggered a comparable immune response to the mice that received the two liquid injections, and a single pellet vaccine should be tested as a novel immunization method for livestock.
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Vacina Antivariólica , Animais , Camundongos , Ácido Palmítico , Adjuvantes Imunológicos , Imunoglobulina G , Imunidade Celular , Vacinas de Subunidades Antigênicas , Ovalbumina , Camundongos Endogâmicos BALB CRESUMO
Climate change adversely affects the yield and productivity of cereal crops, which consequently impacts food security. Therefore, studying stress acclimation, particularly transcriptional patterns and morpho-physiological responses of cereal crops to different stresses, will provide insights into the molecular determinants underlying climate resilience. The availability of advanced tools and approaches has enabled the characterization of plants at morphological, physiological, biochemical, and molecular levels, which will lead to the identification of genomic regions regulating the stress responses at these levels. This will further facilitate using transgenic, breeding, or genome editing approaches to manipulate the identified regions (genes, alleles, or QTLs) to enhance stress resilience. Next-generation sequencing approaches have advanced the identification of causal genes and markers in the genomes through forward or reverse genetics. In this context, the review enumerates the progress of dissecting the molecular mechanisms underlying transcriptional and physiological responses of major cereals to climate-induced stresses. The review systematically discusses different tools and approaches available to study the response of plants to various stresses and identify the molecular determinants regulating stress-resilience. Further, the application of genomics-assisted breeding, transgene-, and targeted editing-based approaches for modulating the genetic determinants for enhanced climate resilience has been elaborated.
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Grão Comestível , Melhoramento Vegetal , Produtos Agrícolas/genética , Grão Comestível/genética , Genômica , Locos de Características Quantitativas/genéticaRESUMO
Millets constitute a significant proportion of underutilized grasses and are well known for their climate resilience as well as excellent nutritional profiles. Among millets, foxtail millet (Setaria italica) and its wild relative green foxtail (S. viridis) are collectively regarded as models for studying broad-spectrum traits, including abiotic stress tolerance, C4 photosynthesis, biofuel, and nutritional traits. Since the genome sequence release, the crop has seen an exponential increase in omics studies to dissect agronomic, nutritional, biofuel, and climate-resilience traits. These studies have provided first-hand information on the structure, organization, evolution, and expression of several genes; however, knowledge of the precise roles of such genes and their products remains elusive. Several open-access databases have also been instituted to enable advanced scientific research on these important crops. In this context, the current review enumerates the contemporary trend of research on understanding the climate resilience and other essential traits in Setaria, the knowledge gap, and how the information could be translated for the crop improvement of related millets, biofuel crops, and cereals. Also, the review provides a roadmap for studying other underutilized crop species using Setaria as a model.
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Now-a-days fungal infection emerges as a significant problem to healthcare management systems due to high frequency of associated morbidity, mortality toxicity, drug-drug interactions, and resistance of the antifungal agents. Aspergillus is the most common mold that cause infection in immunocompromised hosts. It's a hyaline mold that is cosmopolitan and ubiquitous in nature. Aspergillus infects around 10 million population each year with a mortality rate of 30-90%. Clinically available antifungal formulations are restricted to four classes (i.e., polyene, triazole, echinocandin, and allylamine), and each of them have their own limitations associated with the activity spectrum, the emergence of resistance, and toxicity. Consequently, novel antifungal agents with modified and altered chemical structures are required to combat these invasive fungal infections. To overcome these limitations, there is an urgent need for new antifungal agents that can act as potent drugs in near future. Currently, some compounds have shown effective antifungal activity. In this review article, we have discussed all potential antifungal therapies that contain old antifungal drugs, combination therapies, and recent novel antifungal formulations, with a focus on the Aspergillus associated infections.
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Antifúngicos , Aspergilose , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Equinocandinas/uso terapêutico , Micoses/tratamento farmacológicoRESUMO
Fungal infections have shown an upsurge in recent decades, which is mainly because of the increasing number of immunocompromised patients and the occurrence of invasive candidiasis has been found to be 7-15 fold greater than that of invasive aspergillosis. The genus Candida comprises more than 150 distinct species, however, only a few of them are found to be pathogenic to humans. Mortality rates of Candida species are found to be around 45% and the reasons for this intensified mortality are inefficient diagnostic techniques and unfitting initial treatment strategies. There are only a few antifungal drug classes that are employed for the remedy of invasive fungal infections. which include azoles, polyenes, echinocandins, and pyrimidine analogs. During the last 2-3 decades, the usage of antifungal drugs has increased several folds due to which the reports of escalating antifungal drug resistance have also been recorded. The resistance is mostly to the triazole- based compounds. Due to the occurrence of antifungal drug resistance, the success rates of treatment have been reduced as well as major changes have been observed in the frequency of fungal infections. In this review, we have summarized the major molecular mechanisms for the development of antifungal drug resistance.
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Candida , Micoses , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Equinocandinas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológicoRESUMO
An effective single-dose vaccine that protects the dam and her suckling offspring against infectious disease would be widely beneficial to livestock animals. We assessed whether a single-dose intramuscular (i.m.) porcine epidemic diarrhea virus (PEDV) vaccine administered to the gilt 30 days post-breeding could generate mucosal and systemic immunity and sufficient colostral and mature milk antibodies to protect suckling piglets against infectious challenge. The vaccine was comprised of polymeric poly-(lactide-co-glycolide) (PGLA)-nanoparticle (NP) encapsulating recombinant PEDV spike protein 1 (PEDVS1) associated with ARC4 and ARC7 adjuvants, a muramyl dipeptide analog and a monophosphoryl lipid A (MPLA) analog, respectively (NP-PEDVS1). To establish whether prior mucosal exposure could augment the i.m. immune response and/or contribute to mucosal tolerance, gilts were immunized with the NP-PEDVS1 vaccine via the intrauterine route at breeding, followed by the i.m. vaccine 30 days later. Archived colostrum from gilts that were challenged with low-dose PEDV plus alum was used as positive reference samples for neutralizing antibodies and passive protection. On day 100 of gestation (70 days post i.m. immunization), both vaccinated groups showed significant PEDVS1-specific IgG and IgA in the serum, as well as in uterine tissue collected on the day of euthanasia. Anti-PEDVS1 colostral IgG antibody titers collected at farrowing were significantly higher relative to the negative control gilts indicating that the NP vaccine was effective in contributing to the colostral antibodies. The PEDVS1-specific colostral IgA and anti-PEDVS1 IgG and IgA antibodies in the mature milk collected 6 days after farrowing were low for both vaccinated groups. No statistical differences between the vaccinated groups were observed, suggesting that the i.u. priming vaccine did not induce mucosal tolerance. Piglets born to either group of vaccinated gilts did not receive sufficient neutralizing antibodies to protect them against infectious PEDV at 3 days of age. In summary, a single i.m. NP vaccine administered 30 days after breeding and a joint i.u./i.m. vaccine administered at breeding and 30 days post-breeding induced significant anti-PEDVS1 immunity in systemic and mucosal sites but did not provide passive protection in suckling offspring.