RESUMEN

Candida auris has been reported in the past few years as an invasive fungal pathogen of high interest. Its recent emergence in healthcare-associated infections triggered the efforts of researchers worldwide, seeking additional alternatives to the use of traditional antifungals such as azoles. Lipopeptides, specially the echinocandins, have been reported as an effective approach to control pathogenic fungi. However, despite its efficiency against C. auris, some isolates presented echinocandin resistance. Thus, therapies focused on echinocandins' synergism with other antifungal drugs were widely explored, representing a novel possibility for the treatment of C. auris infections.

RESUMEN

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.

Asunto(s)

Microbioma Gastrointestinal , Microbiota , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Disbiosis/tratamiento farmacológico , Humanos

RESUMEN

Bacterial resistance has been listed as one of the main threats to human health, leading to high mortality rates. Among the mechanisms involved in bacterial resistance proliferation and selection, we can cite cross-resistance, which occurs when resistance events to one anti-infective agent trigger resistance to other agents. Thus, considering the importance of cross-resistance evolution worldwide in the context of resistant bacterial infections, this minireview focused on the description of bacterial adaptation, including biofilm formation. Here, we explored the correlation between different anti-infective agents, including antibiotics, metal ions, biocides, and antimicrobial peptides in bacterial cross-resistance, also highlighting the most reported mechanisms of adaptation that accompany this resistance.

Asunto(s)

Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Bacteriana , Biopelículas , Humanos

RESUMEN

This review emphasizes the biotechnological potential of molecules implicated in the different layers of plant immunity, including, pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), effector-triggered susceptibility (ETS), and effector-triggered immunity (ETI) that can be applied in the development of disease-resistant genetically modified (GM) plants. These biomolecules are produced by pathogens (viruses, bacteria, fungi, oomycetes) or plants during their mutual interactions. Biomolecules involved in the first layers of plant immunity, PTI and ETS, include inhibitors of pathogen cell-wall-degrading enzymes (CWDEs), plant pattern recognition receptors (PRRs) and susceptibility (S) proteins, while the ETI-related biomolecules include plant resistance (R) proteins. The biomolecules involved in plant defense PTI/ETI responses described herein also include antimicrobial peptides (AMPs), pathogenesis-related (PR) proteins and ribosome-inhibiting proteins (RIPs), as well as enzymes involved in plant defensive secondary metabolite biosynthesis (phytoanticipins and phytoalexins). Moreover, the regulation of immunity by RNA interference (RNAi) in GM disease-resistant plants is also considered. Therefore, the present review does not cover all the classes of biomolecules involved in plant innate immunity that may be applied in the development of disease-resistant GM crops but instead highlights the most common strategies in the literature, as well as their advantages and disadvantages.

Asunto(s)

Biotecnología , Productos Agrícolas/genética , Enfermedades de las Plantas/inmunología , Inmunidad de la Planta/genética , Proteínas de Plantas/genética , Productos Agrícolas/inmunología , Productos Agrícolas/microbiología , Resistencia a la Enfermedad/genética , Ingeniería Genética , Interacciones Huésped-Patógeno , Enfermedades de las Plantas/microbiología , Plantas Modificadas Genéticamente , Interferencia de ARN , Receptores de Reconocimiento de Patrones/genética

RESUMEN

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.

Asunto(s)

Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Farmacorresistencia Bacteriana , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/fisiología , Animales , Humanos

RESUMEN

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.

Asunto(s)

Glándulas Exocrinas/metabolismo , Proteínas de Peces/genética , Venenos de los Peces/metabolismo , Rajidae/metabolismo , Animales , Brasil , Agua Dulce , Perfilación de la Expresión Génica , Hialuronoglucosaminidasa/genética , Rajidae/genética , Especificidad de la Especie

RESUMEN

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.

Asunto(s)

Flores/genética , Flores/metabolismo , Transcriptoma/genética , Zantedeschia/genética , Secuencia de Aminoácidos , Antiinfecciosos/farmacología , Proteínas Portadoras/química , Ritmo Circadiano/genética , Ambiente , Escherichia coli/efectos de los fármacos , Flores/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Ligandos , Pruebas de Sensibilidad Microbiana , Simulación de Dinámica Molecular , Datos de Secuencia Molecular , Reguladores del Crecimiento de las Plantas/metabolismo , Inmunidad de la Planta/efectos de los fármacos , Inmunidad de la Planta/genética , Metabolismo Secundario/efectos de los fármacos , Metabolismo Secundario/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Staphylococcus aureus/efectos de los fármacos , Extractos de Tejidos , Transcripción Genética/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Zantedeschia/efectos de los fármacos , Zantedeschia/inmunología

RESUMEN

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.

Asunto(s)

Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Proteómica , Bacterias/genética , Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Fenómenos Fisiológicos Bacterianos/genética , Membrana Celular/efectos de los fármacos , Humanos , Proteómica/métodos

RESUMEN

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⁻¹), 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.

Asunto(s)

Antibacterianos/farmacología , Citosol/fisiología , Farmacorresistencia Bacteriana/genética , Escherichia coli/efectos de los fármacos , Magaininas/farmacología , Proteoma/genética , Aminoácidos/metabolismo , Pared Celular/metabolismo , Pared Celular/ultraestructura , Simulación por Computador , Electroforesis en Gel de Poliacrilamida , Metabolismo Energético/genética , Fermentación , Pruebas de Sensibilidad Microbiana , Nitrógeno/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrometría de Masas en Tándem

RESUMEN

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.

Asunto(s)

Antibacterianos/química , Antibacterianos/farmacología , Regulación de la Expresión Génica de las Plantas/fisiología , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/química , Proteínas de Plantas/farmacología , Descubrimiento de Drogas , Humanos , Enfermedades de las Plantas/inmunología , Proteínas de Plantas/genética