RESUMO
The need for new antimicrobial therapies is evident, especially to reduce antimicrobial resistance and minimize deleterious effects on gut microbiota. However, although diverse studies discuss the adverse effects of broad-spectrum antibiotics on the microbiome ecology, targeted interventions that could solve this problem have often been overlooked. The impact of antibiotics on gut microbiota homeostasis is alarming, compromising its microbial community and leading to changes in host health. Recent studies have shown that these impacts can be transient or permanent, causing irreversible damage to gut microbiota. The responses to and changes in the gut microbial community arising from antibiotic treatment are related to its duration, the number of doses, antibiotic class, host age, genetic susceptibility, and lifestyle. In contrast, each individual's native microbiota can also affect the response to treatment as well as respond differently to antibiotic treatment. In this context, the current challenge is to promote the growth of potentially beneficial microorganisms and to reduce the proportion of microorganisms that cause dysbiosis, thus contributing to an improvement in the patient's health. An essential requirement for the development of novel antibiotics will be personalized medicinal strategies that recognize a patient's intestinal and biochemical individuality. Thus, this Review will address a new perspective on antimicrobial therapies through pathogen-selective antibiotics that minimize the impacts on human health due to changes in the gut microbiota from the use of antibiotics.
Assuntos
Microbioma Gastrointestinal , Microbiota , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Disbiose/tratamento farmacológico , HumanosRESUMO
The ability of pathogenic bacteria to aggregate and form biofilm represents a great problem for public health, since they present extracellular components that encase these micro-organisms, making them more resistant to antibiotics and host immune attack. This may become worse when antibiotic-resistant bacterial strains form biofilms. However, antibiofilm screens with different compounds may reveal potential therapies to prevent/treat biofilm infections. Here, we focused on Klebsiella pneumoniae, an opportunistic bacterium that causes different types of infections, including in the bloodstream, meninges, lungs, urinary system and at surgical sites. We also highlight aspects involved in the formation and maintenance of K. pneumoniae biofilms, as well as resistance and the emergence of new trends to combat this health challenge.
Assuntos
Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/fisiologia , Animais , HumanosRESUMO
Stingrays commonly cause human envenoming related accidents in populations of the sea, near rivers and lakes. Transcriptomic profiles have been used to elucidate components of animal venom, since they are capable of providing molecular information on the biology of the animal and could have biomedical applications. In this study, we elucidated the transcriptomic profile of the venom glands from two different freshwater stingray species that are endemic to the Paraná-Paraguay basin in Brazil, Potamotrygon amandae and Potamotrygon falkneri. Using RNA-Seq, we identified species-specific transcripts and overlapping proteins in the venom gland of both species. Among the transcripts related with envenoming, high abundance of hyaluronidases was observed in both species. In addition, we built three-dimensional homology models based on several venom transcripts identified. Our study represents a significant improvement in the information about the venoms employed by these two species and their molecular characteristics. Moreover, the information generated by our group helps in a better understanding of the biology of freshwater cartilaginous fishes and offers clues for the development of clinical treatments for stingray envenoming in Brazil and around the world. Finally, our results might have biomedical implications in developing treatments for complex diseases.
Assuntos
Glândulas Exócrinas/metabolismo , Proteínas de Peixes/genética , Venenos de Peixe/metabolismo , Rajidae/metabolismo , Animais , Brasil , Água Doce , Perfilação da Expressão Gênica , Hialuronoglucosaminidase/genética , Rajidae/genética , Especificidade da EspécieRESUMO
Zantedeschia aethiopica is an evergreen perennial plant cultivated worldwide and commonly used for ornamental and medicinal purposes including the treatment of bacterial infections. However, the current understanding of molecular and physiological mechanisms in this plant is limited, in comparison to other non-model plants. In order to improve understanding of the biology of this botanical species, RNA-Seq technology was used for transcriptome assembly and characterization. Following Z. aethiopica spathe tissue RNA extraction, high-throughput RNA sequencing was performed with the aim of obtaining both abundant and rare transcript data. Functional profiling based on KEGG Orthology (KO) analysis highlighted contigs that were involved predominantly in genetic information (37%) and metabolism (34%) processes. Predicted proteins involved in the plant circadian system, hormone signal transduction, secondary metabolism and basal immunity are described here. In silico screening of the transcriptome data set for antimicrobial peptide (AMP) -encoding sequences was also carried out and three lipid transfer proteins (LTP) were identified as potential AMPs involved in plant defense. Spathe predicted protein maps were drawn, and suggested that major plant efforts are expended in guaranteeing the maintenance of cell homeostasis, characterized by high investment in carbohydrate, amino acid and energy metabolism as well as in genetic information.
Assuntos
Flores/genética , Flores/metabolismo , Transcriptoma/genética , Zantedeschia/genética , Sequência de Aminoácidos , Anti-Infecciosos/farmacologia , Proteínas de Transporte/química , Ritmo Circadiano/genética , Meio Ambiente , Escherichia coli/efeitos dos fármacos , Flores/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Ligantes , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Reguladores de Crescimento de Plantas/metabolismo , Imunidade Vegetal/efeitos dos fármacos , Imunidade Vegetal/genética , Metabolismo Secundário/efeitos dos fármacos , Metabolismo Secundário/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Staphylococcus aureus/efeitos dos fármacos , Extratos de Tecidos , Transcrição Gênica/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Zantedeschia/efeitos dos fármacos , Zantedeschia/imunologiaRESUMO
Antibiotics are important therapeutic agents commonly used for the control of bacterial infectious diseases; however, resistance to antibiotics has become a global public health problem. Therefore, effective therapy in the treatment of resistant bacteria is necessary and, to achieve this, a detailed understanding of mechanisms that underlie drug resistance must be sought. To fill the multiple gaps that remain in understanding bacterial resistance, proteomic tools have been used to study bacterial physiology in response to antibiotic stress. In general, the global analysis of changes in the protein composition of bacterial cells in response to treatment with antibiotic agents has made it possible to construct a database of proteins involved in the process of resistance to drugs with similar mechanisms of action. In the past few years, progress in using proteomic tools has provided the most realistic picture of the infective process, since these tools detect the end products of gene biosynthetic pathways, which may eventually determine a biological phenotype. In most bacterial species, alterations occur in energy and nitrogen metabolism regulation; glucan biosynthesis is up-regulated; amino acid, protein, and nucleotide synthesis is affected; and various proteins show a stress response after exposing these microorganisms to antibiotics. These issues have been useful in identifying targets for the development of novel antibiotics and also in understanding, at the molecular level, how bacteria resist antibiotics.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Proteômica , Bactérias/genética , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Fenômenos Fisiológicos Bacterianos/genética , Membrana Celular/efeitos dos fármacos , Humanos , Proteômica/métodosRESUMO
Antimicrobial peptides (AMPs) are effective antibiotic agents commonly found in plants, animals, and microorganisms, and they have been suggested as the future of antimicrobial chemotherapies. It is vital to understand the molecular details that define the mechanism of action of resistance to AMPs for a rational planning of the next antibiotic generation and also to shed some light on the complex AMP mechanism of action. Here, the antibiotic resistance of Escherichia coli ATCC 8739 to magainin I was evaluated in the cytosolic subproteome. Magainin-resistant strains were selected after 10 subsequent spreads at subinhibitory concentrations of magainin I (37.5 mg · liter⻹), and their cytosolic proteomes were further compared to those of magainin-susceptible strains through two-dimensional electrophoresis analysis. As a result, 41 differentially expressed proteins were detected by in silico analysis and further identified by tandem mass spectrometry de novo sequencing. Functional categorization indicated an intense metabolic response mainly in energy and nitrogen uptake, stress response, amino acid conversion, and cell wall thickness. Indeed, data reported here show that resistance to cationic antimicrobial peptides possesses a greater molecular complexity than previously supposed, resulting in cell commitment to several metabolic pathways.
Assuntos
Antibacterianos/farmacologia , Citosol/fisiologia , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Magaininas/farmacologia , Proteoma/genética , Aminoácidos/metabolismo , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Simulação por Computador , Eletroforese em Gel de Poliacrilamida , Metabolismo Energético/genética , Fermentação , Testes de Sensibilidade Microbiana , Nitrogênio/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em TandemRESUMO
Storage proteins perform essential roles in plant survival, acting as molecular reserves important for plant growth and maintenance, as well as being involved in defense mechanisms by virtue of their properties as insecticidal and antimicrobial proteins. These proteins accumulate in storage vacuoles inside plant cells, and, in response to determined signals, they may be used by the different plant tissues in response to pathogen attack. To shed some light on these remarkable proteins with dual functions, storage proteins found in germinative tissues, such as seeds and kernels, and in vegetative tissues, such as tubercles and leaves, are extensively discussed here, along with the related mechanisms of protein expression. Among these proteins, we focus on 2S albumins, Kunitz proteinase inhibitors, plant lectins, glycine-rich proteins, vicilins, patatins, tarins, and ocatins. Finally, the potential use of these molecules in development of drugs to combat human and plant pathogens, contributing to the development of new biotechnology-based medications and products for agribusiness, is also presented.