Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
Más filtros

Intervalo de año de publicación
1.
Cancer ; 129(14): 2122-2127, 2023 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-37081639

RESUMEN

Despite significant progress in the early detection, treatment, and survivorship of cancer in recent decades, cancer disparities continue to plague segments of the US population. Many of these cancer disparities, especially those among historically marginalized racial and ethnic groups and those with lower socioeconomic resources, are caused and perpetuated by social and structural barriers to health. These social and structural barriers, which operate beyond the framework of cancer control, also systematically increase vulnerability to and decrease adaptive capacity for the deleterious effects of anthropogenic climate change. The established and emerging overlap between climate vulnerability and cancer risk presents complex challenges to cancer control, specifically among populations who suffer compounding hazards and intersectional vulnerabilities. By embracing these intersections, we may be able to conceptualize promising new research frameworks and programmatic opportunities that decrease vulnerability to a wide range of climate and health threats to advance health equity.


Asunto(s)
Cambio Climático , Neoplasias , Humanos , Riesgo , Neoplasias/epidemiología
2.
Med Mycol ; 61(7)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37410609

RESUMEN

The species of the Candida genus are opportunistic pathogenic fungi found in humans and are responsible for ∼80% of worldwide fungal infections. Aimed at diminishing and preventing Candida adhesion to cells or implanted devices in the human host, a large diversity of materials has been developed and functionalized that have attracted much interest. Furthermore, these materials have been focused almost exclusively on Candida albicans, followed by C. glabrata, C. parapsilosis, and C. tropicalis. Although an important diversity of materials has been synthesized to prevent adherence and formation of biofilms by Candida species, it is however important to evaluate the capacity of each material in terms of its property to diminish the adherence of Candida. These materials are discussed in this review.


Asunto(s)
Candida albicans , Candida , Animales , Humanos , Biopelículas , Candida glabrata , Antifúngicos
3.
Antonie Van Leeuwenhoek ; 115(4): 505-519, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35175437

RESUMEN

The most frequently isolated human fungal pathogen is Candida albicans which is responsible for about 50% of all Candida infections. In healthy individuals, this organism resides as a part of the normal microbiota in equilibrium with the host. However, under certain conditions, particularly in immunocompromised patients, this opportunistic pathogen adheres to host cells causing serious systemic infections. Thus, much effort has been dedicated to the study of its physiology with emphasis on factors associated to pathogenicity. A representative analysis deals with the mechanisms of glycoprotein assembly as many cell surface antigens and other macromolecules that modulate the immune system fall within this chemical category. In this regard, studies of the terminal protein glycosylation stage which occurs in Golgi vesicles has led to the identification of nucleotidases that convert glycosyltransferase-generated dinucleotides into the corresponding mononucleotides, thus playing a double function: their activity prevent inhibition of further glycosyl transfer by the accumulation of dinucleotides and the resulting mononucleotides are exchanged by specific membrane transporters for equimolecular amounts of sugar donors from the cytosol. Here, using a simple protocol for protein separation we isolated a bifunctional nucleotidase from C. albicans active on GDP and UDP that was characterized in terms of its molecular mass, response to bivalent ions and other factors, substrate specificity and affinity. Results are discussed in terms of the similarities and differences of this nucleotidase with similar counterparts from other organisms thus contributing to the knowledge of a bifunctional diphosphatase not described before in C. albicans.


Asunto(s)
Candida albicans , Candidiasis , Humanos , Pirofosfatasas/metabolismo
4.
Microb Pathog ; 161(Pt B): 105270, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34793878

RESUMEN

Sporothrix schenckii is a dimorphic fungus, pathogenic to humans and animals, which is usually infective in the yeast form. Reactive oxygen species (ROS) play an important role in the host's defense, damaging the pathogen's DNA, proteins, and lipids. To prevent oxidative damage, the ROS are detoxified by pathogen-derived antioxidant enzymes such as catalases (CATs). In this work, we analyzed the activity and expression level of three S. schenckii genes, designated as CAT1, CAT2, and CAT3, that putatively encoded for three isoforms of monofunctional CAT with a predicted molecular weight of 57.6, 56.2, and 81.4 kDa, respectively. Our results demonstrate that oxidative stress induced by exogenous H2O2 leads to an altered lipid peroxidation, modifying CAT activity and the expression levels of the CAT genes, being CAT1 and CAT3 the genes with the highest expression in response to the oxidizing agent. These results show that CAT isoforms in S. schenckii can be regulated in response to oxidative stress and might help to control ROS homeostasis in the fungus-host interaction.


Asunto(s)
Sporothrix , Esporotricosis , Animales , Catalasa/genética , Catalasa/metabolismo , Peróxido de Hidrógeno , Estrés Oxidativo , Sporothrix/genética , Esporotricosis/veterinaria
5.
Arch Microbiol ; 203(5): 2219-2228, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33630118

RESUMEN

Candida genus comprises several species that can be found in the oral cavity and the gastrointestinal and genitourinary tracts of healthy individuals. Under certain conditions, however, they behave as opportunistic pathogens that colonize these tissues, most frequently when the immune system is compromised by a disease or under certain medical treatments. To colonize the human host, these organisms require to express cell wall proteins (CWP) that allowed them to adhere and adapt to the reactive oxygen (ROS) and nitrogen (RNS) species produced in the macrophage during the respiratory burst. The aim of this study was to determine how four Candida species respond to the oxidative stress imposed by cumene hydroperoxide (CHP). To this purpose, C. albicans, C. glabrata, C. krusei and C. parapsilosis were exposed to this oxidant which is known to generate ROS in the membrane phospholipids. Accordingly, both mock and CHP-exposed cells were used to extract and analyze CWP and also to measure catalase activity and the levels of protein carbonylation. Results indicated that all four species express different CWP to neutralize ROS. Most relevant among these proteins were the glycolytic enzymes enolase and glyceraldehyde-3-phosphate dehydrogenase, known as moonlight proteins because in addition to participate in glycolysis they play an important role in the cell response to ROS. In addition, a thiol-specific antioxidant enzyme (Tsa) was also found to counteract ROS.


Asunto(s)
Derivados del Benceno/farmacología , Candida/clasificación , Candida/metabolismo , Oxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/metabolismo , Candida/enzimología , Pared Celular/metabolismo , Tracto Gastrointestinal/microbiología , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Humanos , Macrófagos/inmunología , Boca/microbiología , Fosfopiruvato Hidratasa/metabolismo , Proteómica , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sistema Urogenital/microbiología
6.
Antonie Van Leeuwenhoek ; 114(5): 609-624, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33660079

RESUMEN

It is well documented that disturbance of cell surface by some agents triggers compensatory responses aimed to maintain the cell wall integrity in fungi and other organisms. Here, the thermodimorphic fungus Sporothrix globosa, a member of the pathogenic clade of the Sporothrix complex, was propagated in yeast-peptone-dextrose medium under conditions to obtain the mycelium (pH 4.5, 27-28 °C) or the yeast (pH 7.8, 32-34 °C) morphotypes in the absence and presence of the wall-interacting dyes Congo Red (CR) and Calcofluor White (CFW) either alone or in combination. After different periods of time, growth, cell morphology and activity of glucosamine-6-phosphate synthase (GlcN-6-P synthase), an ubiquitous enzyme that plays a crucial role in cell wall biogenesis, were determined. CR and to a lower extent CFW affected growth and morphology of both fungal morphotypes and significantly increased enzyme activity. Notoriously, CR or CR in combination with CFW induced the transient conversion of yeasts into conidia-forming filamentous cells even under culture conditions adjusted for yeast development, most likely as a strategy to evade the noxious effect of the dye. After sometime, hypha returned to yeast cells. An hypothetical model to explain the effect of CR on morphology and enzyme activity based on the possible role of membrane-spanning proteins known as mechanosensors is proposed. Results are discussed in terms of the fungal responses to cell wall damage.


Asunto(s)
Sporothrix , Bencenosulfonatos , Pared Celular , Rojo Congo
7.
Microb Pathog ; 141: 103987, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31962184

RESUMEN

Sporotrichosis is an emergent subcutaneous mycosis that is a threat to both humans and other animals. Sporotrichosis is acquired by the traumatic implantation of species of the Sporothrix genus. Added to the detoxification systems, pathogenic fungi possess different mechanisms that allow them to survive within the phagocytic cells of their human host during the oxidative burst. These mechanisms greatly depend from the cell wall (CW) since phagocytic cells recognize pathogens through specific receptors associated to the structure. To date, there are no studies addressing the modulation of the expression of S. schenckii CW proteins (CWP) in response to reactive oxygen species (ROS). Therefore, in this work, a proteomic analysis of the CW of S. schenckii in response to the oxidative agent menadione (O2•-) was performed. Proteins that modulate their expression were identified which can be related to the fungal survival mechanisms within the phagocyte. Among the up-regulated CWP in response to the oxidative agent, 13 proteins that could be involved in the mechanisms of oxidative stress response in S. schenckii were identified. The proteins identified were thioredoxin1 (Trx1), superoxide dismutase (Sod), GPI-anchored cell wall protein, ß-1,3-endoglucanase EglC, glycoside hydrolase (Gh), chitinase, CFEM domain protein, glycosidase crf1, covalently-linked cell wall protein (Ccw), 30 kDa heat shock protein (Hsp30), lipase, trehalase (Treh), fructose-bisphosphate aldolase (Fba1) and citrate synthase (Cs). The identification of CWP that modulates their expression in response to superoxide ion (O2•-) in S. schenckii is a useful approach to understand how the fungus defends itself against ROS, in order to evade the phagocytic cells from the host and cause the infection.


Asunto(s)
Pared Celular/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sporothrix , Vitamina K 3/farmacología , Animales , Pared Celular/química , Enfermedades Transmisibles Emergentes/inmunología , Enfermedades Transmisibles Emergentes/microbiología , Proteínas Fúngicas/análisis , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Genoma Fúngico , Evasión Inmune , Oxidantes/farmacología , Estrés Oxidativo/fisiología , Fagocitos/inmunología , Fagocitos/microbiología , Proteómica , Sporothrix/efectos de los fármacos , Sporothrix/genética , Sporothrix/metabolismo , Esporotricosis/inmunología
8.
Cell Commun Signal ; 18(1): 111, 2020 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-32653010

RESUMEN

BACKGROUND: Cells taken from mouse embryos before sex differentiation respond to insults according to their chromosomal sex, a difference traceable to differential methylation. We evaluated the mechanism for this difference in the controlled situation of their response to ethanol. METHODS: We evaluated the expression of mRNA for alcohol dehydrogenase (ADH), aldehyde dehyrogenases (ALDH), and a cytochrome P450 isoenzyme (Cyp2e1) in male and female mice, comparing the expressions to toxicity under several experimental conditions evaluating redox and other states. RESULTS: Females are more sensitive to ethanol. Disulfiram, which inhibits alcohol dehydrogenase (ADH), increases cell death in males, eliminating the sex dimorphism. The expressions ADH Class 1 to 4 and ALDH Class 1 and 2 do not differ by sex. However, females express approximately 8X more message for Cyp2e1, an enzyme in the non-canonical pathway. Female cells produce approximately 15% more ROS (reactive oxygen species) than male cells, but male cells contain approximately double the concentration of GSH, a ROS scavenger. Scavenging ROS with N-acetyl cysteine reduces cell death and eliminates sex dimorphism. Finally, since many of the differences in gene expression derive from methylation of DNA, we exposed cells to the methyltransferase inhibitor 5-aza- 2-deoxycytidine; blocking methylation eliminates both the difference in expression of Cyp2e1 and cell death. CONCLUSION: We conclude that the sex-differential cell death caused by ethanol derives from sex dimorphic methylation of Cyp2e1 gene, resulting in generation of more ROS.


Asunto(s)
Citocromo P-450 CYP2E1/metabolismo , Metilación de ADN/genética , Etanol/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Acetilcisteína/farmacología , Alcohol Deshidrogenasa/genética , Alcohol Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Animales , Azacitidina/farmacología , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocromo P-450 CYP2E1/genética , Metilación de ADN/efectos de los fármacos , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , Modelos Biológicos , Isoformas de Proteínas/metabolismo , Caracteres Sexuales , Estrés Fisiológico/efectos de los fármacos , Transcripción Genética/efectos de los fármacos
9.
Arch Microbiol ; 201(1): 135-141, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30302500

RESUMEN

Sporothrix schenckii is the etiological agent of sporotrichosis, a mycosis of humans and other mammals. Little is known about the responses of this thermodimorphic pathogen to perturbations in the cell wall (CW) by different stress conditions. Here we describe the effect of Congo Red (CR) on the fungal growth, morphogenesis and activity of glucosamine-6-phosphate (GlcN-6-P) synthase. Under conditions of yeast development, 15 µM CR abolished conidia (CN) germination, but when yeast cells were first obtained in the absence of the dye and then post-incubated in its presence, yeasts rapidly differentiated into mycelial cells. On the other hand, under conditions of mycelium development, 150 µM CR did not affect CN germination, but filamentous cells underwent structural changes characterized by a distorted CW contour, the loss of polarity and the formation of red-pigmented, hyphal globose structures. Under these conditions, CR also induced a significant and transient increase in the activity of GlcN-6-P synthase, an essential enzyme in CW biogenesis.


Asunto(s)
Rojo Congo/farmacología , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora)/metabolismo , Sporothrix/crecimiento & desarrollo , Sporothrix/metabolismo , Animales , Pared Celular/química , Humanos , Hifa/crecimiento & desarrollo , Micelio/crecimiento & desarrollo , Sporothrix/enzimología , Esporotricosis/microbiología
10.
Microb Pathog ; 124: 21-29, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30118801

RESUMEN

In recent years, C. albicans and C. glabrata have been identified as the main cause of candidemia and invasive candidiasis in hospitalized and immunocompromised patients. In order to colonize the human host, these fungi express several virulence factors such as the response to oxidative stress and the formation of biofilms. In the expression of these virulence factors, the cell wall of C. albicans and C. glabrata is of fundamental importance. As the outermost structure of the yeast, the cell wall is the first to come in contact with the reactive oxygen species (ROS) generated during the respiratory outbreak, and in the formation of biofilms, it is the first to adhere to organs or medical devices implanted in the human host. In both processes, several cell wall proteins (CWP) are required, since they promote attachment to human cells or abiotic surfaces, as well as to detoxify ROS. In our working group we have identified moonlighting CWP in response to oxidative stress as well as in the formation of biofilms. Having identified moonlighting CWP in Candida species in response to two virulence factors indicates that these proteins may possibly be immunodominant. The aim of the present work was to evaluate whether proteins of this type such as fructose-bisphosphate aldolase (Fba1), phosphoglycerate kinase (Pgk) and pyruvate kinase (Pk), could confer protection in a mouse model against C. albicans and C. glabrata. For this, recombinant proteins His6-Fba1, His6-Pgk and His6-Pk were constructed and used to immunize several groups of mice. The immunized mice were infected with C. albicans or C. glabrata, and subsequently the liver, spleen and kidney were extracted and the number of CFU was determined. Our results showed that Pk confers immunity to mice against C. albicans, while Fba1 to C. glabrata. This data allows us to conclude that the moonlighting CWP, Fba1 and Pk confer in vivo protection in a specific way against each species of Candida. This makes them promising candidates for developing specific vaccines against these pathogens.


Asunto(s)
Candidiasis/prevención & control , Fructosa-Bifosfato Aldolasa/inmunología , Proteínas Fúngicas/inmunología , Vacunas Fúngicas/inmunología , Fosfoglicerato Quinasa/inmunología , Piruvato Quinasa/inmunología , Animales , Candida albicans/inmunología , Candida glabrata/inmunología , Candidiasis/inmunología , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Fructosa-Bifosfato Aldolasa/administración & dosificación , Proteínas Fúngicas/administración & dosificación , Vacunas Fúngicas/administración & dosificación , Riñón/microbiología , Hígado/microbiología , Ratones , Fosfoglicerato Quinasa/administración & dosificación , Piruvato Quinasa/administración & dosificación , Bazo/microbiología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología
11.
Microb Pathog ; 107: 293-303, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28396240

RESUMEN

Adhesion is the first step for Candida species to form biofilms on medical devices implanted in the human host. Both the physicochemical nature of the biomaterial and cell wall proteins (CWP) of the pathogen play a determinant role in the process. While it is true that some CWP have been identified in vitro, little is known about the CWP of pathogenic species of Candida involved in adhesion. On this background, we considered it important to investigate the potential role of CWP of C. albicans, C. glabrata, C. krusei and C. parapsilosis in adhesion to different medical devices. Our results indicate that the four species strongly adher to polyvinyl chloride (PVC) devices, followed by polyurethane and finally by silicone. It was interesting to identify fructose-bisphosphate aldolase (Fba1) and enolase 1 (Eno1) as the CWP involved in adhesion of C. albicans, C. glabrata and C. krusei to PVC devices whereas phosphoglycerate kinase (Pgk) and Eno1 allow C. parapsilosis to adher to silicone-made implants. Results presented here suggest that these CWP participate in the initial event of adhesion and are probably followed by other proteins that covalently bind to the biomaterial thus providing conditions for biofilm formation and eventually the onset of infection.


Asunto(s)
Candida/fisiología , Adhesión Celular , Pared Celular/química , Equipos y Suministros/microbiología , Proteínas de la Membrana/aislamiento & purificación , Proteínas de la Membrana/fisiología , Antifúngicos/farmacología , Materiales Biocompatibles/química , Biopelículas/crecimiento & desarrollo , Candida/efectos de los fármacos , Candida/enzimología , Candida/metabolismo , Adhesión Celular/efectos de los fármacos , Pared Celular/enzimología , Pared Celular/metabolismo , Fructosa-Bifosfato Aldolasa/aislamiento & purificación , Fructosa-Bifosfato Aldolasa/fisiología , Proteínas Fúngicas/fisiología , Humanos , Peróxido de Hidrógeno/farmacología , Fosfoglicerato Quinasa , Fosfopiruvato Hidratasa/aislamiento & purificación , Fosfopiruvato Hidratasa/fisiología , Poliuretanos/química , Cloruro de Polivinilo/química , Siliconas/química
12.
Microb Pathog ; 90: 22-33, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26550764

RESUMEN

Biofilms of Candida species are associated with high morbidity and hospital mortality. Candida forms biofilms by adhering to human host epithelium through cell wall proteins (CWP) and simultaneously neutralizing the reactive oxygen species (ROS) produced during the respiratory burst by phagocytic cells. The purpose of this paper is to identify the CWP of Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis expressed after exposure to different concentrations of H2O2 using a proteomic approach. CWP obtained from sessile cells, both treated and untreated with the oxidizing agent, were resolved by one and two-dimensional (2D-PAGE) gels and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Some of these proteins were identified and found to correspond to moonlighting CWP such as: (i) glycolytic enzymes, (ii) heat shock, (iii) OSR proteins, (iv) general metabolic enzymes and (v) highly conserved proteins, which are up- or down-regulated in the presence or absence of ROS. We also found that the expression of these CWP is different for each Candida species. Moreover, RT-PCR assays allowed us to demonstrate that transcription of the gene coding for Eno1, one of the moonlight-like CWP identified in response to the oxidant agent, is differentially regulated. To our knowledge this is the first demonstration that, in response to oxidative stress, each species of Candida, differentially regulates the expression of moonlighting CWP, which may protect the organism from the ROS generated during phagocytosis. Presumptively, these proteins allow the pathogen to adhere and form a biofilm, and eventually cause invasive candidiasis in the human host. We propose that, in addition to the antioxidant mechanisms present in Candida, the moonlighting CWP also confer protection to these pathogens from oxidative stress.


Asunto(s)
Biopelículas , Candida/fisiología , Pared Celular/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas de la Membrana/metabolismo , Estrés Oxidativo/fisiología , Antioxidantes/metabolismo , Biopelículas/crecimiento & desarrollo , Candida/efectos de los fármacos , Candida/enzimología , Candida/metabolismo , Pared Celular/efectos de los fármacos , Pared Celular/enzimología , Proteínas Fúngicas/genética , Regulación Enzimológica de la Expresión Génica , Regulación Fúngica de la Expresión Génica , Proteínas de Choque Térmico/metabolismo , Humanos , Peróxido de Hidrógeno/farmacología , Proteínas de la Membrana/genética , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo
13.
Microb Pathog ; 87: 1-12, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26188289

RESUMEN

In order for Candida species to adhere and colonize human host cells they must express cell wall proteins (CWP) and adapt to reactive oxygen species (ROS) generated by phagocytic cells of the human host during the respiratory burst. However, how these pathogens change the expression of CWP in response to oxidative stress (OSR) is not known. Here, fifteen moonlight-like CWP were identified that expressed differentially in four species of Candida after they were exposed to H2O2 or menadione (O2(-)). These proteins included: (i) glycolytic enzymes, such as glyceraldehyde-3-phosphate dehydrogenase (Gapdh), fructose-bisphosphate aldolase (Fba1), phosphoglycerate mutase (Gpm1), phosphoglycerate kinase (Pgk), pyruvate kinase (Pk) and enolase (Eno1); (ii) the heat shock proteins Ssb1 and Ssa2; (iii) OSR proteins such as peroxyredoxin (Tsa1), the stress protein Ddr48 (Ddr48) and glutathione reductase (Glr1); (iv) other metabolic enzymes such as ketol-acid reductoisomerase (Ilv5) and pyruvate decarboxylase (Pdc1); and (v) other proteins such as elongation factor 1-beta (Efb1) and the 14-3-3 protein homolog. RT-PCR revealed that transcription of the genes coding for some of the identified CWP are differentially regulated. To our knowledge this is the first report showing that moonlight-like CWP are the first line of defense of Candida against ROS, and that they are differentially regulated in each of these pathogens.


Asunto(s)
Candida/química , Candida/efectos de los fármacos , Pared Celular/química , Proteínas Fúngicas/análisis , Oxidantes/metabolismo , Estrés Oxidativo , Proteoma/análisis , Candida/genética , Candida/fisiología , Proteínas Fúngicas/genética , Perfilación de la Expresión Génica , Humanos , Peróxido de Hidrógeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vitamina K 3/metabolismo
14.
Curr Microbiol ; 69(5): 733-9, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25002360

RESUMEN

Invasive candidiasis is associated with high mortality in immunocompromised and hospitalized patients. Candida albicans is the main pathological agent followed by Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis. These pathogens colonize different host tissues in humans as they are able to neutralize the reactive species generated from nitrogen and oxygen during the respiratory burst. Among the enzymatic mechanisms that Candida species have developed to protect against free radicals are enzymes with antioxidant and immunodominant functions such as flavohemoglobins, catalases, superoxide dismutases, glutathione reductases, thioredoxins, peroxidases, heat-shock proteins, and enolases. These mechanisms are under transcriptional regulation by factors such as Cta4p, Cwt1p, Yap1p, Skn7p, Msn2p, and Msn4p. However, even though it has been proposed that all Candida species have similar enzymatic systems, it has been observed that they respond differentially to various types of stress. These differential responses may explain the colonization of different organs by each species. Here, we review the enzymatic mechanisms developed by C. albicans and C. glabrata species in response to oxidative and nitrosative stresses. Lack of experimental information for other pathogenic species limits a comparative approach among different organisms.


Asunto(s)
Candida albicans/efectos de los fármacos , Candida albicans/fisiología , Candida glabrata/efectos de los fármacos , Candida glabrata/fisiología , Compuestos Nitrosos/toxicidad , Oxidantes/toxicidad , Estrés Fisiológico , Redes y Vías Metabólicas/genética
15.
Microbiol Mol Biol Rev ; 88(2): e0015823, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38551349

RESUMEN

SUMMARYThe metabolic conditions that prevail during bacterial growth have evolved with the faithful operation of repair systems that recognize and eliminate DNA lesions caused by intracellular and exogenous agents. This idea is supported by the low rate of spontaneous mutations (10-9) that occur in replicating cells, maintaining genome integrity. In contrast, when growth and/or replication cease, bacteria frequently process DNA lesions in an error-prone manner. DNA repairs provide cells with the tools needed for maintaining homeostasis during stressful conditions and depend on the developmental context in which repair events occur. Thus, different physiological scenarios can be anticipated. In nutritionally stressed bacteria, different components of the base excision repair pathway may process damaged DNA in an error-prone approach, promoting genetic variability. Interestingly, suppressing the mismatch repair machinery and activating specific DNA glycosylases promote stationary-phase mutations. Current evidence also suggests that in resting cells, coupling repair processes to actively transcribed genes may promote multiple genetic transactions that are advantageous for stressed cells. DNA repair during sporulation is of interest as a model to understand how transcriptional processes influence the formation of mutations in conditions where replication is halted. Current reports indicate that transcriptional coupling repair-dependent and -independent processes operate in differentiating cells to process spontaneous and induced DNA damage and that error-prone synthesis of DNA is involved in these events. These and other noncanonical ways of DNA repair that contribute to mutagenesis, survival, and evolution are reviewed in this manuscript.


Asunto(s)
Bacillus subtilis , Reparación del ADN , Mutagénesis , Reparación del ADN/genética , Bacillus subtilis/genética , Bacillus subtilis/fisiología , Estrés Fisiológico/genética , Daño del ADN , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Replicación del ADN , ADN Bacteriano/genética , Esporas Bacterianas/genética , Esporas Bacterianas/crecimiento & desarrollo
16.
ACS Omega ; 8(32): 29585-29594, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37599928

RESUMEN

Understanding the origin of life on our planet has generated diverse theories. Currently, the theory is that life has a single origin; however, its starting point has not been defined. As evidenced, it is indispensable to unify the different theories to reach a single theory that would also allow linking the different areas of knowledge to finally understand the mechanism by which life originated on Earth. In this regard, aiming at contributing to the unification of the diverse theories on the origin of life, in this work, the hypothesis based on the condition that silica-carbonates of alkaline earth metals, called biomorphs, are the ones that could unify all the proposed theories on the origin of life is proposed. Aimed at evaluating if this hypothesis is viable, this work assessed whether biomorphs are able to protect the DNA from continuous UV radiation under two conditions that emulate the habitats that could have co-existed in the Precambrian and, after the radiation, evaluated the time during which DNA remained inside the biomorphs. Our results showed that biomorphs can protect the DNA for months after continuous UV exposure. It was also determined that biomorphs protect the DNA from external factors in different habitats, like normal atmospheric conditions and in aqueous environments. The obtained data allowed me to infer that biomorphs may be the gap that unifies the diverse proposed theories on the origin of life in our Planet.

17.
ISA Trans ; 139: 713-723, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37295999

RESUMEN

Different works in literature have reported that nonlinear controllers based on the energy approach are not effective to completely swing-up an inverted pendulum subjected to friction. Most studies trying to solve this issue consider static friction models in the design of controllers. This consideration is mainly because the stability proof of the system with dynamic friction in closed-loop is difficult. Hence, this paper presents a nonlinear controller with friction compensation to swing-up a Furuta pendulum with dynamic friction. With this aim, we consider that only the active joint of the system is subjected to friction, which is represented via a dynamic model, namely, the Dahl model. We first present Furuta Pendulum dynamic model with dynamic friction. Then, by slightly modifying an energy-based controller that has been previously reported in literature and by including friction compensation, we propose a nonlinear controller that allows to swing-up completely a Furuta pendulum subjected to friction. The unmeasurable friction state is estimated through a nonlinear observer and a stability analysis of the closed-loop system is accomplished with the direct Lyapunov method. Finally, successful experimental results are presented for a Furuta pendulum prototype built by authors. This shows the effectiveness of the proposed controller in achieving a complete swing-up of the Furuta pendulum, in a time feasible for experimental implementation, and ensuring closed-loop stability.

18.
J Fungi (Basel) ; 9(9)2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37755027

RESUMEN

Glycoside hydrolases (GHs) are enzymes that participate in many biological processes of fungi and other organisms by hydrolyzing glycosidic linkages in glycosides. They play fundamental roles in the degradation of carbohydrates and the assembly of glycoproteins and are important subjects of studies in molecular biology and biochemistry. Based on amino acid sequence similarities and 3-dimensional structures in the carbohydrate-active enzyme (CAZy), they have been classified in 171 families. Members of some of these families also exhibit the activity of trans-glycosydase or glycosyl transferase (GT), i.e., they create a new glycosidic bond in a substrate instead of breaking it. Fungal glycosidases are important for virulence by aiding tissue adhesion and colonization, nutrition, immune evasion, biofilm formation, toxin release, and antibiotic resistance. Here, we review fungal glycosidases with a particular emphasis on Sporothrix species and C. albicans, two well-recognized human pathogens. Covered issues include a brief account of Sporothrix, sporotrichosis, the different types of glycosidases, their substrates, and mechanism of action, recent advances in their identification and characterization, their potential biotechnological applications, and the limitations and challenges of their study given the rather poor available information.

19.
Front Cell Infect Microbiol ; 12: 976924, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36211971

RESUMEN

The cell wall (CW) of fungi exhibits a complex structure and a characteristic chemical composition consisting almost entirely of interacting crystalline and amorphous polysaccharides. These are synthesized by a number of sugar polymerases and depolymerases encoded by a high proportion of the fungal genome (for instance, 20% in Saccharomyces cerevisiae). These enzymes act in an exquisitely coordinated process to assemble the tridimensional and the functional structure of the wall. Apart from playing a critical role in morphogenesis, cell protection, viability and pathogenesis, the CW represents a potential target for antifungals as most of its constituents do not exist in humans. Chitin, ß-glucans and cellulose are the most frequent crystalline polymers found in the fungal CW. The hexosamine biosynthesis pathway (HBP) is critical for CW elaboration. Also known as the Leloir pathway, this pathway ends with the formation of UDP-N-GlcNAc after four enzymatic steps that start with fructose-6-phosphate and L-glutamine in a short deviation of glycolysis. This activated aminosugar is used for the synthesis of a large variety of biomacromolecules in a vast number of organisms including bacteria, fungi, insects, crustaceans and mammalian cells. The first reaction of the HBP is catalyzed by GlcN-6-P synthase (L-glutamine:D-fructose-6-phosphate amidotransferase; EC 2.6.1.16), a critical enzyme that has been considered as a potential target for antifungals. The enzyme regulates the amount of cell UDP-N-GlcNAc and in eukaryotes is feedback inhibited by the activated aminosugar and other factors. The native and recombinant forms of GlcN-6-P synthase has been purified and characterized from both prokaryotic and eukaryotic organisms and demonstrated its critical role in CW remodeling and morphogenesis after exposure of some fungi to agents that stress the cell surface by interacting with wall polymers. This review deals with some of the cell compensatory responses of fungi to wall damage induced by Congo Red and Calcofluor White.


Asunto(s)
Sporothrix , beta-Glucanos , Animales , Antifúngicos , Bencenosulfonatos , Pared Celular/metabolismo , Celulosa , Quitina , Rojo Congo , Glutamina , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora)/genética , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora)/metabolismo , Hexosaminas/análisis , Hexosaminas/metabolismo , Humanos , Mamíferos/metabolismo , Polímeros/análisis , Sporothrix/metabolismo , Azúcares , Uridina Difosfato , beta-Glucanos/análisis
20.
Comput Ind Eng ; 168: 108125, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35370350

RESUMEN

The pandemic by COVID-19 is causing a devastating effect on the health of the global population. Currently, there are several efforts to prevent the spread of the virus. Among those efforts, cleaning and disinfecting public areas have become important tasks and they should be automated in future smart cities. To contribute in this direction, this paper proposes a coverage path planning method for a spraying drone, an unmanned aerial vehicle that has mounted a sprayer/sprinkler system, that can disinfect areas. State-of-the-art planners consider a camera instead of a sprinkler, in consequence, the expected coverage will differ in running time because the liquid dispersion is different from a camera's projection model. In addition, current planners assume that the vehicles can fly outside the target region; this assumption can not be satisfied in our problem, because disinfections are performed at low altitudes. Our method presents i) a new sprayer/sprinkler model that fits a more realistic coverage volume to the drop dispersion and ii) a planning method that efficiently restricts the flight to the region of interest avoiding potential collisions in bounded scenes. The algorithm has been tested in several simulation scenes, showing that it is effective and covers more areas with respect to two approaches in the literature. Note that the proposal is not limited to disinfection applications, but can be applied to other ones, such as painting or precision agriculture.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA