RESUMEN
The delay in making a correct diagnosis of Candida auris causes concern in the healthcare system setting, and immunoproteomics studies are important to identify immunoreactive proteins for new diagnostic strategies. In this study, immunocompetent murine systemic infections caused by non-aggregative and aggregative phenotypes of C. auris and by Candida albicans and Candida haemulonii were carried out, and the obtained sera were used to study their immunoreactivity against C. auris proteins. The results showed higher virulence, in terms of infection signs, weight loss, and histopathological damage, of the non-aggregative isolate. Moreover, C. auris was less virulent than C. albicans but more than C. haemulonii. Regarding the immunoproteomics study, 13 spots recognized by sera from mice infected with both C. auris phenotypes and analyzed by mass spectrometry corresponded to enolase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase. These four proteins were also recognized by sera obtained from human patients with disseminated C. auris infection but not by sera obtained from mice infected with C. albicans or Aspergillus fumigatus. Spot identification data are available via ProteomeXchange with the identifier PXD049077. In conclusion, this study showed that the identified proteins could be potential candidates to be studied as new diagnostic or even therapeutic targets for C. auris.
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Candida , Candidiasis , Inmunoglobulina G , Animales , Ratones , Candida/inmunología , Candida/patogenicidad , Humanos , Candidiasis/inmunología , Candidiasis/microbiología , Candidiasis/sangre , Inmunoglobulina G/sangre , Antígenos Fúngicos/inmunología , Antígenos Fúngicos/sangre , Proteómica/métodos , Candida albicans/inmunología , Candida albicans/patogenicidad , Proteínas Fúngicas/inmunología , Fosfoglicerato Mutasa/inmunología , Fosfoglicerato Quinasa/inmunología , Gliceraldehído-3-Fosfato Deshidrogenasas/inmunología , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Anticuerpos Antifúngicos/sangre , Anticuerpos Antifúngicos/inmunología , Femenino , VirulenciaRESUMEN
In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.
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Biomarcadores , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/inmunología , AnimalesRESUMEN
Immune disorders arise from complex genetic and environmental factors, which lead to dysregulation at the cellular and inflammatory levels and cause tissue damage. Recent research highlights the crucial role of reactive antibodies in autoimmune diseases and graft rejection, but their complex determination poses challenges for clinical use. Therefore, our study aimed to ascertain whether the presence of reactive antibodies against membrane antigens in tissues from both animal models and humans could serve as biomarkers in patients with autoimmune disorders. To address this issue, we examined the binding profile of serological antibodies against a diverse panel of cell membranes from the spleen, liver, and kidney tissues of monkeys, rats, and humans. After developing the cell membrane microarrays, human sera were immunologically assayed. The study was first conducted on sera from two groups, healthy subjects and patients with inflammatory and autoimmune disorders, and then optimized for kidney transplant patient sera. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in patients' serum as potential biomarkers of immune disorders. However, it is important to note that these results need to be verified in further studies with a larger sample size to confirm their relevance.
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Nefritis Lúpica , Bazo , Humanos , Ratas , Animales , Antígenos , Hígado , Autoanticuerpos , Riñón , Rechazo de InjertoRESUMEN
INTRODUCTION: Quantitative reverse transcription PCR (RT-qPCR) is the leading tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given that it will almost certainly continue to coexist with other respiratory viruses in the coming years, our study aimed to design a multiplex PCR system not affected by supplier outages and with reduced cost compared to the existing commercially available kits. METHODS AND RESULTS: In this study, combinations of four primers/probe sets were used to construct a flexible RT-qPCR assay which is capable of discriminating between SARS-CoV-2 and the seasonal human coronavirus HCoV-OC43, or even influenza A virus. Additionally, the human RPP30 gene was used as an internal control. To demonstrate the robustness of the assay, it was applied to a collection of 150 clinical samples. The results showed 100% sensitivity and specificity compared to the automatized system used at the hospital and were better when indeterminate samples were analysed. CONCLUSIONS: This study provides an efficient method for the simultaneous detection of SARS-CoV-2, HCoV-OC43 and influenza A virus, and its efficacy has been tested on clinical samples showing outstanding results. SIGNIFICANCE AND IMPACT OF THE STUDY: The multiplex RT-qPCR design offers an accessible and economical alternative to commercial detection kits for hospitals and laboratories with limited economic resources or facing situations of supply shortage.
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COVID-19 , Virus de la Influenza A , Humanos , SARS-CoV-2/genética , Reacción en Cadena de la Polimerasa Multiplex/métodos , Virus de la Influenza A/genética , COVID-19/diagnóstico , Sensibilidad y Especificidad , NasofaringeRESUMEN
Lomentospora (Scedosporium) prolificans is an opportunistic pathogen capable of causing invasive infections in immunocompromised patients. The fungus is able to disseminate via the bloodstream finally arriving at the central nervous system producing neurological symptoms and, in many cases, patient death. In this context, microglial cells, which are the resident immune cells in the central nervous system, may play an important role in these infections. However, this aspect of anti-L. prolificans immunity has been poorly researched to date. Thus, the interactions and activity of microglial cells against L. prolificans were analysed, and the results show that there was a remarkable impairment in their performance regarding phagocytosis, the development of oxidative burst, and in the production of pro-inflammatory cytokines, compared with macrophages. Interestingly, L. prolificans displays great growth also when challenged with immune cells, even when inside them. We also proved that microglial phagocytosis of the fungus is highly dependent on mannose receptor and especially on dectin-1. Taken together, these data provide evidence for an impaired microglial response against L. prolificans and contribute to understanding the pathobiology of its neurotropism.
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Interacciones Huésped-Patógeno , Evasión Inmune , Microglía/inmunología , Microglía/microbiología , Scedosporium/inmunología , Scedosporium/patogenicidad , Animales , Células Cultivadas , Citocinas/metabolismo , Macrófagos/inmunología , Macrófagos/microbiología , Ratones , Fagocitosis , Estallido Respiratorio , Scedosporium/crecimiento & desarrolloRESUMEN
Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.
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Antifúngicos/uso terapéutico , Ascomicetos/fisiología , Farmacorresistencia Fúngica Múltiple/genética , Micosis/microbiología , Scedosporium/fisiología , Antifúngicos/farmacología , Ascomicetos/clasificación , Ascomicetos/efectos de los fármacos , Ascomicetos/genética , Terapia Combinada , Ecología , Interacciones Huésped-Patógeno/inmunología , Humanos , Huésped Inmunocomprometido , Tipificación Molecular , Micosis/diagnóstico , Micosis/patología , Micosis/terapia , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/patología , Infecciones Oportunistas/terapia , Scedosporium/clasificación , Scedosporium/efectos de los fármacos , Scedosporium/genética , Procedimientos Quirúrgicos Operativos , Factores de VirulenciaRESUMEN
Energy-dense foods and overnutrition represent major starting points altering lipid metabolism, systemic inflammation and gut microbiota. The aim of this work was to investigate the effects of a high-fat diet (HFD) over a period of 25 days on intestinal microbiota and inflammation in zebrafish. Microbial composition of HFD-fed animals was analysed and compared to controls by 16S rRNA sequencing and quantitative PCR. The expression level on several genes related to inflammation was tested. Furthermore, microscopic assessment of the intestine was performed in both conditions. The consumption of the HFD resulted in microbial dysbiosis, characterised by an increase in the relative abundance of the phylum Bacteroidetes. Moreover, an emerging intestinal inflammation via NF-κß activation was confirmed by the overexpression of several genes related to signalling receptors, antimicrobial metabolism and the inflammatory cascade. The intestinal barrier was also damaged, with an increase of goblet cell mucin production. This is the first study performed in zebrafish which suggests that the consumption of a diet enriched with 10% fat changes the intestinal microbial community composition, which was correlated with low-grade inflammation.
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Dieta Alta en Grasa/efectos adversos , Disbiosis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación , Intestinos/microbiología , Animales , Antiinfecciosos/metabolismo , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/genética , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Células Caliciformes/metabolismo , Sistema Inmunológico , Intestinos/patología , Mucinas/metabolismo , ARN Ribosómico 16S/genética , Pez Cebra/inmunología , Pez Cebra/microbiologíaRESUMEN
Cystic fibrosis (CF) is a genetic disorder that increases the risk of suffering microbial, including fungal, infections. In this paper, proteomics-based information was collated relating to secreted and cell wall proteins with potential medical applications from the most common filamentous fungi in CF, i.e., Aspergillus and Scedosporium/Lomentospora species. Among the Aspergillus fumigatus secreted allergens, ß-1,3-endoglucanase, the alkaline protease 1 (Alp1/oryzin), Asp f 2, Asp f 13/15, chitinase, chitosanase, dipeptidyl-peptidase V (DppV), the metalloprotease Asp f 5, mitogillin/Asp f 1, and thioredoxin reductase receive a special mention. In addition, the antigens ß-glucosidase 1, catalase, glucan endo-1,3-ß-glucosidase EglC, ß-1,3-glucanosyltransferases Gel1 and Gel2, and glutaminase A were also identified in secretomes of other Aspergillus species associated with CF: Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, and Aspergillus terreus. Regarding cell wall proteins, cytochrome P450 and eEF-3 were proposed as diagnostic targets, and alkaline protease 2 (Alp2), Asp f 3 (putative peroxiredoxin pmp20), probable glycosidases Asp f 9/Crf1 and Crf2, GPI-anchored protein Ecm33, ß-1,3-glucanosyltransferase Gel4, conidial hydrophobin Hyp1/RodA, and secreted aspartyl protease Pep2 as protective vaccines in A. fumigatus. On the other hand, for Scedosporium/Lomentospora species, the heat shock protein Hsp70 stands out as a relevant secreted and cell wall antigen. Additionally, the secreted aspartyl proteinase and an ortholog of Asp f 13, as well as the cell wall endo-1,3-ß-D-glucosidase and 1,3-ß-glucanosyl transferase, were also found to be significant proteins. In conclusion, proteins mentioned in this review may be promising candidates for developing innovative diagnostic and therapeutic tools for fungal infections in CF patients.
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Aspergillus/química , Proteínas Fúngicas/análisis , Proteoma/análisis , Proteómica/métodos , Scedosporium/química , Alérgenos/análisis , Antígenos Fúngicos/análisis , Pared Celular/química , Fibrosis Quística/microbiología , HumanosRESUMEN
The filamentous fungus Lomentospora prolificans is an emerging pathogen causing severe infections mainly among the immunocompromised population. These diseases course with high mortality rates due to great virulence of the fungus, its inherent resistance to available antifungals, and absence of specific diagnostic tools. Despite being widespread in humanized environments, L. prolificans rarely causes infections in immunocompetent individuals likely due to their developed protective immune response. In this study, conidial and hyphal immunomes against healthy human serum IgG were analyzed, identifying immunodominant antigens and establishing their prevalence among the immunocompetent population. Thirteen protein spots from each morph were detected as reactive against at least 70% of serum samples, and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hence, the most seroprevalent antigens were WD40 repeat 2 protein, malate dehydrogenase, and DHN1, in conidia, and heat shock protein (Hsp) 70, Hsp90, ATP synthase ß subunit, and glyceraldehyde-3-phosphate dehydrogenase, in hyphae. More interestingly, the presence of some of these seroprevalent antigens was determined on the cell surface, as Hsp70, enolase, or Hsp90. Thus, we have identified a diverse set of antigenic proteins, both in the entire proteome and cell surface subproteome, which may be used as targets to develop innovative therapeutic or diagnostic tools.
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Ascomicetos/inmunología , Proteínas Fúngicas/metabolismo , Micosis/inmunología , Proteoma/metabolismo , Proteómica/métodos , Antígenos Fúngicos/inmunología , Antígenos Fúngicos/metabolismo , Ascomicetos/fisiología , Cromatografía Liquida , Electroforesis en Gel Bidimensional , Técnica del Anticuerpo Fluorescente Indirecta , Proteínas Fúngicas/inmunología , Interacciones Huésped-Patógeno/inmunología , Humanos , Hifa/inmunología , Hifa/metabolismo , Immunoblotting , Inmunocompetencia/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Micosis/sangre , Micosis/microbiología , Proteoma/inmunología , Esporas Fúngicas/inmunología , Esporas Fúngicas/metabolismo , Espectrometría de Masas en TándemRESUMEN
There is currently increasing concern about the relation between microbial infections and cancer. More and more studies support the view that there is an association, above all, when the causal agents are bacteria or viruses. This review adds to this, summarizing evidence that the opportunistic fungus Candida albicans increases the risk of carcinogenesis and metastasis. Until recent years, Candida spp. had fundamentally been linked to cancerous processes as it is an opportunist pathogen that takes advantage of the immunosuppressed state of patients particularly due to chemotherapy. In contrast, the most recent findings demonstrate that C. albicans is capable of promoting cancer by several mechanisms, as described in the review: production of carcinogenic byproducts, triggering of inflammation, induction of Th17 response and molecular mimicry. We underline the need not only to control this type of infection during cancer treatment, especially given the major role of this yeast species in nosocomial infections, but also to find new therapeutic approaches to avoid the pro-tumor effect of this fungal species.
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Candida albicans/fisiología , Candidiasis/complicaciones , Neoplasias/epidemiología , Neoplasias/etiología , Candidiasis/inmunología , Candidiasis/metabolismo , Candidiasis/microbiología , Carcinógenos/metabolismo , Adhesión Celular , Transformación Celular Neoplásica , Progresión de la Enfermedad , Humanos , Inmunidad Innata , Inflamación/complicaciones , Inflamación/metabolismo , Inflamación/microbiología , Metástasis de la Neoplasia , Neoplasias/patología , Receptores de Reconocimiento de Patrones/metabolismo , Transducción de SeñalRESUMEN
Aspergillus fumigatus is considered to be the most prevalent airborne pathogenic fungus and can cause invasive diseases in immunocompromised patients. It is known that its virulence is multifactorial, although the mechanisms of pathogenicity remain unclear. With the aim of improving our understanding of these mechanisms, we designed a new expression microarray covering the entire genome of A. fumigatus. In this first study, we analysed the transcriptomes of this fungus at the first steps of germination after being grown at 24 and 37 °C. The microarray data revealed that 1249 genes were differentially expressed during growth at these two temperatures. According to our results, A. fumigatus modified significantly the expression of genes related to metabolism to adapt to new conditions. The high percentages of genes that encoded hypothetical or unclassified proteins differentially expressed implied that many as yet unknown genes were involved in the establishment of A. fumigatus infection. Furthermore, amongst the genes implicated in virulence upregulated at 37 °C on the microarray, we found those that encoded proteins mainly related to allergens (Asp F1, Asp F2 and MnSOD), gliotoxin biosynthesis (GliP and GliZ), nitrogen (NiiA and NiaD) or iron (HapX, SreA, SidD and SidC) metabolism. However, gene expression in iron and nitrogen metabolism might be influenced not only by heat shock, but also by the availability of nutrients in the medium, as shown by the addition of fresh medium.
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Aspergilosis/microbiología , Aspergillus fumigatus/metabolismo , Proteínas Fúngicas/genética , Esporas Fúngicas/crecimiento & desarrollo , Transcriptoma , Aspergillus fumigatus/genética , Aspergillus fumigatus/crecimiento & desarrollo , Proteínas Fúngicas/metabolismo , Perfilación de la Expresión Génica , Regulación Fúngica de la Expresión Génica , Calor , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Esporas Fúngicas/genética , Esporas Fúngicas/metabolismoRESUMEN
In this study, two distinct in vitro infection models of Aspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated A. fumigatus uncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously published in vivo transcriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, the maiA gene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption of maiA resulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of ß-glucans within the cell wall but did not show lack of chitin or mannans. The maiA-1 mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking the A. fumigatus maiA gene to fungal cell wall homeostasis and virulence.
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Aspergillus fumigatus , Proteínas Fúngicas , Animales , Humanos , Ratones , Aspergillus fumigatus/metabolismo , Pared Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Homeostasis , Virulencia/genéticaRESUMEN
The liver, and more specifically, the liver sinusoidal endothelial cells, constitute the beginning of one of the most important responses for the elimination of hematogenously disseminated Candida albicans. Therefore, we aimed to study the mechanisms involved in the interaction between these cells and C. albicans. Transcriptomics-based analysis showed an increase in the expression of genes related to the immune response (including receptors, cytokines, and adhesion molecules), as well as to aerobic glycolysis. Further in vitro analyses showed that IL-6 production in response to C. albicans is controlled by MyD88- and SYK-pathways, suggesting an involvement of Toll-like and C-type lectin receptors and the subsequent activation of the MAP-kinases and c-Fos/AP-1 transcription factor. In addition, liver sinusoidal endothelial cells undergo metabolic reprogramming towards aerobic glycolysis induced by C. albicans, as confirmed by the increased Extracellular Acidification Rate and the overexpression of enolase (Eno2), hexonikase (Hk2) and glucose transporter 1 (Slc2a1). In conclusion, these results indicate that the hepatic endothelium responds to C. albicans by increasing aerobic glycolysis and promoting an inflammatory environment.
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Candida albicans , Células Endoteliales , Glucólisis , Hígado , Candida albicans/inmunología , Células Endoteliales/metabolismo , Células Endoteliales/microbiología , Animales , Hígado/metabolismo , Hígado/microbiología , Quinasa Syk/metabolismo , Interleucina-6/metabolismo , Interleucina-6/genética , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , Inflamación/metabolismo , Perfilación de la Expresión Génica , Candidiasis/inmunología , Candidiasis/microbiología , Candidiasis/metabolismoRESUMEN
Invasive aspergillosis (IA) is a serious nosocomial infection caused by Aspergillus spp. which has a high mortality rate due to the fact, among other factors, that it is difficult to diagnose. Within the Aspergillus genus, A. fumigatus is the main species causing IA. We propose a virulence factor, the aspHS gene, as a novel target for the specific detection of A. fumigatus by quantitative real-time PCR (qPCR). This target gene encodes a haemolysin, which is overexpressed in vivo during infection. We have designed specific primers and hydrolysis (Taqman) probes for the detection of this target and a chimeric internal amplification control (IC), designed to detect false negative results due to PCR inhibition. This qPCR assay was tested with DNA extracted from a wide collection of microorganisms, tissues from infected mice, and human bronchoalveolar lavage (BAL) samples. Results showed that it, together with the DNA extraction method, could detect A. fumigatus with high specificity. Furthermore, it can distinguish between germinated (first step to the development of infection) and non-germinated conidia (not detected). Our data indicate that these techniques could be sufficiently sensitive and rapid to help clinicians establish an earlier diagnosis, but the presence of PCR inhibitors in clinical samples such as BAL fluids needs to be addressed.
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Aspergilosis/diagnóstico , Aspergillus fumigatus/aislamiento & purificación , Proteínas Fúngicas/genética , Técnicas de Diagnóstico Molecular/métodos , Micología/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Factores de Virulencia/genética , Animales , Aspergillus fumigatus/genética , Cartilla de ADN/genética , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Técnicas de Diagnóstico Molecular/normas , Micología/normas , Sondas de Oligonucleótidos/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Sensibilidad y EspecificidadRESUMEN
The detection of Scedosporium/Lomentospora is still based on non-standardized low-sensitivity culture procedures. This fact is particularly worrying in patients with cystic fibrosis (CF), where these fungi are the second most common filamentous fungi isolated, because a poor and delayed diagnosis can worsen the prognosis of the disease. To contribute to the discovery of new diagnostic strategies, a rapid serological dot immunobinding assay (DIA) that allows the detection of serum IgG against Scedosporium/Lomentospora in less than 15 min was developed. A crude protein extract from the conidia and hyphae of Scedosporium boydii was employed as a fungal antigen. The DIA was evaluated using 303 CF serum samples (162 patients) grouped according to the detection of Scedosporium/Lomentospora in the respiratory sample by culture, obtaining a sensitivity and specificity of 90.48% and 79.30%, respectively; positive and negative predictive values of 54.81% and 96.77%, and an efficiency of 81.72%. The clinical factors associated with the results were also studied using a univariate and a multivariate analysis, which showed that Scedosporium/Lomentospora positive sputum, elevated anti-Aspergillus serum IgG and chronic Pseudomonas aeruginosa infection were significantly associated with a positive result in DIA, while Staphylococcus aureus positive sputum showed a negative association. In conclusion, the test developed can offer a complementary, rapid, simple and sensitive method to contribute to the diagnosis of Scedosporium/Lomentospora in patients with CF.
RESUMEN
The most common genetic hereditary disease affecting Caucasians is cystic fibrosis (CF), which is caused by autosomal recessive mutations in the CFTR gene. The most serious consequence is the production of a thick and sticky mucus in the respiratory tract, which entraps airborne microorganisms and facilitates colonization, inflammation and infection. Therefore, the present article compiles the information about the microbiota and, particularly, the inter-kingdom fungal-bacterial interactions in the CF lung, the molecules involved and the potential effects that these interactions may have on the course of the disease. Among the bacterial compounds, quorum sensing-regulated molecules such as homoserine lactones, phenazines, rhamnolipids, quinolones and siderophores (pyoverdine and pyochelin) stand out, but volatile organic compounds, maltophilin and CF-related bacteriophages are also explained. These molecules exhibit diverse antifungal mechanisms, including iron starvation and induction of reactive oxygen and nitrogen species production. The fungal compounds are less studied, but they include cell wall components, siderophores, patulin and farnesol. Despite the apparent competition between microorganisms, the persistence of significant rates of bacterial-fungal co-colonization in CF suggests that numerous variables influence it. In conclusion, it is crucial to increase scientific and economic efforts to intensify studies on the bacterial-fungal inter-kingdom interactions in the CF lung.
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Fibrosis Quística , Microbiota , Humanos , Fibrosis Quística/genética , Fibrosis Quística/microbiología , Sideróforos , Bacterias , Pulmón/microbiologíaRESUMEN
Many species of Alternaria are important pathogens that cause plant diseases and postharvest rots. They lead to significant economic losses in agriculture and affect human and animal health due to their capacity to produce mycotoxins. Therefore, it is necessary to study the factors that can result in an increase in A. alternata. In this study, we discuss the mechanism by which phenol content protects from A. alternata, since the red oak leaf cultivar (containing higher phenols) showed lower invasion than the green one, Batavia, and no mycotoxin production. A climate change scenario enhanced fungal growth in the most susceptible cultivar, green lettuce, likely because elevated temperature and CO2 levels decrease plant N content, modifying the C/N ratio. Finally, while the abundance of the fungi was maintained at similar levels after keeping the lettuces for four days at 4 °C, this postharvest handling triggered TeA and TEN mycotoxin synthesis, but only in the green cultivar. Therefore, the results demonstrated that invasion and mycotoxin production are cultivar- and temperature-dependent. Further research should be directed to search for resistant cultivars and effective postharvest strategies to reduce the toxicological risk and economic losses related to this fungus, which are expected to increase in a climate change scenario.
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Systemic candidiasis remains a major complication among patients suffering from hematological malignancies and favors the development of hepatic metastasis. To contribute to the understanding of the underlying mechanisms, the aim of this study was to identify molecules that may increase tumor cell adhesion to hepatic endothelial cells. To this end, a well-established in vitro model was used to determine the enhancement of tumor cell adhesion induced by Candida albicans and its fractions. Different fractions were obtained according to their molecular weight (M(r)) (five) or to their isoelectric point (pI) (four), using preparative electrophoresis and preparative isoelectric focusing, respectively, followed by affinity chromatography. The fraction that most enhanced melanoma cell adhesion to endothelium had an M(r) range from 45 to 66 kDa. It was characterized using two-dimensional electrophoresis, and 14 proteins were identified by peptide mass fingerprinting: Dor14p, Fba1p, Pdi1p, Pgk1p, Idh2p, Mpg1p, Sfa1p, Ape3p, Ilv5p, Tuf1p, Act1p, Eno1p, Qcr2p, and Adh1p. Of these, several are related to the immunogenic response, and the latter seven belonged to the most reactive fraction according to their pI range, from 5 to 5.6. These findings could represent a step forward in the search for new targets, to suppress the pro-metastatic effect of C. albicans.
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Candida albicans/química , Adhesión Celular/efectos de los fármacos , Endotelio/efectos de los fármacos , Proteínas Fúngicas/aislamiento & purificación , Hígado/citología , Línea Celular Tumoral , Fraccionamiento Químico , Cromatografía de Afinidad , Electroforesis , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Humanos , Focalización Isoeléctrica , Punto Isoeléctrico , Peso MolecularRESUMEN
Infections caused by the opportunistic pathogens Scedosporium/Lomentospora are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review collates information published on immune response against these fungi, since an understanding of the mechanisms involved is of great interest in developing more effective strategies against them. Scedosporium/Lomentospora cell wall components, including peptidorhamnomannans (PRMs), α-glucans and glucosylceramides, are important immune response activators following their recognition by TLR2, TLR4 and Dectin-1 and through receptors that are yet unknown. After recognition, cytokine synthesis and antifungal activity of different phagocytes and epithelial cells is species-specific, highlighting the poor response by microglial cells against L. prolificans. Moreover, a great number of Scedosporium/Lomentospora antigens have been identified, most notably catalase, PRM and Hsp70 for their potential medical applicability. Against host immune response, these fungi contain evasion mechanisms, inducing host non-protective response, masking fungal molecular patterns, destructing host defense proteins and decreasing oxidative killing. In conclusion, although many advances have been made, many aspects remain to be elucidated and more research is necessary to shed light on the immune response to Scedosporium/Lomentospora.
RESUMEN
Aspergillus fumigatus is a ubiquitous soil decomposer and an opportunistic pathogen that is characterized by its large metabolic machinery for acquiring nutrients from media. Lately, an ever-increasing number of genes involved in fungal nutrition has been associated with its virulence. Of these, nitrogen, iron, and zinc metabolism-related genes are particularly noteworthy, since 78% of them have a direct implication in virulence. In this review, we describe the sensing, uptake and regulation process of the acquisition of these nutrients, the connections between pathways and the virulence-implicated genes. Nevertheless, only 40% of the genes mentioned in this review have been assayed for roles in virulence, leaving a wide field of knowledge that remains uncertain and might offer new therapeutic and diagnostic targets.