RESUMEN
The COVID-19 pandemic turned the SARS-CoV-2 into the main target of scientific research all around the world. Many advances have already been made, but there is still a long way to go to solve the molecular mechanisms related to the process of the SARS-CoV-2 infection, as well as the particularities of the disease, its course and the complex host-pathogen relationships. However, a lot has been theorized and associated with COVID-19, like the worst prognosis of the disease among individuals with some comorbidities, like diabetes mellitus. In this perspective, diabetic patients are repeatedly associated with more severe cases of COVID-19 when compared to non-diabetic patients. Even though ACE2 (angiotensin-converting enzyme 2) was recognized as the host cell receptor for both binding and entering of SARS-CoV-2 particles, it was also pointed out that this enzyme plays an important protective role against pulmonary damage. Therefore, paradoxically as it may seem, the low baseline level of this receptor in diabetics is directly linked to a more expressive loss of ACE2 protective effect, which could be one of the possible factors for the worst prognosis of COVID-19. Still, COVID-19 may also have a diabetogenic effect. From this point of view, the main topics that will be highlighted are (i) the mechanism of the viral entry, with special attention to the cellular receptor (ACE2) and the viral binding protein (spike), (ii) the relationship among the renin-angiotensin system, the infection process and the patients' prognosis, (iii) the glucose control and the medicines used in this event, and (iv) a brief analysis on diabetes triggered by COVID-19.
Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/complicaciones , Complicaciones de la Diabetes/metabolismo , COVID-19/metabolismo , COVID-19/virología , Humanos , SARS-CoV-2/aislamiento & purificaciónAsunto(s)
Enfermedades Transmisibles/enzimología , Alveolados/efectos de los fármacos , Alveolados/patogenicidad , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Bacterias/efectos de los fármacos , Bacterias/patogenicidad , Enfermedades Transmisibles/tratamiento farmacológico , Enfermedades Transmisibles/patología , Farmacorresistencia Microbiana , Euglenozoos/efectos de los fármacos , Euglenozoos/patogenicidad , Hongos/efectos de los fármacos , Hongos/patogenicidad , Humanos , Péptido Hidrolasas/química , Péptido Hidrolasas/metabolismo , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , Virulencia/efectos de los fármacosRESUMEN
Pseudallescheria boydii is a filamentous fungus that causes a wide array of infections that can affect practically all the organs of the human body. The treatment of pseudallescheriosis is difficult since P. boydii exhibits intrinsic resistance to the majority of antifungal drugs used in the clinic and the virulence attributes expressed by this fungus are unknown. The study of the secretion of molecules is an important approach for understanding the pathogenicity of fungi. With this task in mind, we have shown that mycelial cells of P. boydii were able to actively secrete proteins into the extracellular environment; some of them were recognized by antibodies present in the serum of a patient with pseudallescheriosis. Additionally, molecules secreted by P. boydii induced in vitro irreversible damage in pulmonary epithelial cells. Subsequently, two-dimensional gel electrophoresis combined with mass spectrometry was carried out in order to start the construction of a map of secreted proteins from P. boydii mycelial cells. The two-dimensional map showed that most of the proteins (around 100 spots) were focused at pH ranging from 4 to 7 with molecular masses ranging from 14 to >117 kDa. Fifty spots were randomly selected, of which 30 (60%) were consistently identified, while 20 (40%) spots generated peptides that showed no resemblance to any known protein from other fungi and/or MS with low quality. Notably, we identified proteins involved in metabolic pathways (energy/carbohydrate, nucleotide, and fatty acid), cell wall remodeling, RNA processing, signaling, protein degradation/nutrition, translation machinery, drug elimination and/or detoxification, protection against environmental stress, cytoskeleton/movement proteins, and immunogenic molecules. Since the genome of this fungus is not sequenced, we performed enzymatic and immunodetection assays in order to corroborate the presence of some released proteins. The identification of proteins actively secreted by P. boydii provides important new information for understanding immune modulation and provides important new perspectives on the biology of this intriguing fungus.
Asunto(s)
Proteínas Fúngicas/metabolismo , Genoma Fúngico , Micelio/metabolismo , Micosis/microbiología , Proteoma/metabolismo , Pseudallescheria/metabolismo , Secuencia de Aminoácidos , Anticuerpos Antifúngicos/sangre , Antígenos Fúngicos/inmunología , Línea Celular Tumoral , Electroforesis en Gel Bidimensional , Proteínas Fúngicas/química , Proteínas Fúngicas/inmunología , Proteínas Fúngicas/farmacología , Humanos , Concentración 50 Inhibidora , Viabilidad Microbiana , Datos de Secuencia Molecular , Micelio/crecimiento & desarrollo , Micelio/inmunología , Micelio/ultraestructura , Micosis/sangre , Fragmentos de Péptidos/química , Mapeo Peptídico , Proteoma/química , Proteoma/inmunología , Proteoma/farmacología , Proteómica , Pseudallescheria/crecimiento & desarrollo , Pseudallescheria/inmunología , Pseudallescheria/ultraestructuraRESUMEN
In this work two-dimensional gel electrophoresis combined with mass spectrometry was carried out in order to start the construction of a map of soluble proteins from epimastigote form of Trypanosoma cruzi CL Brener. This strain is a hybrid organism derived from two genotypes, T. cruzi I and T. cruzi II and was chosen for genome sequencing. The two-dimensional gel electrophoresis showed that most of proteins focused at 4-7 pH range. The identification demonstrated that several proteins were in multiple isoforms, such as tubulin and heat shock proteins. Potential targets for development of chemotherapeutic agents like arginine kinase, an enzyme absent from mammalian tissues that is involved in the energy supply of the parasite, were also detected.