Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 139
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
Annu Rev Genet ; 57: 275-296, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-37708420

RESUMO

Antibiotic resistance genes predate the therapeutic uses of antibiotics. However, the current antimicrobial resistance crisis stems from our extensive use of antibiotics and the generation of environmental stressors that impose new selective pressure on microbes and drive the evolution of resistant pathogens that now threaten human health. Similar to climate change, this global threat results from human activities that change habitats and natural microbiomes, which in turn interact with human-associated ecosystems and lead to adverse impacts on human health. Human activities that alter our planet at global scales exacerbate the current resistance crisis and exemplify our central role in large-scale changes in which we are both protagonists and architects of our success but also casualties of unanticipated collateral outcomes. As cognizant participants in this ongoing planetary experiment, we are driven to understand and find strategies to curb the ongoing crises of resistance and climate change.


Assuntos
Farmacorresistência Bacteriana , Microbiota , Humanos , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Microbiota/genética
2.
J Immunol ; 206(2): 335-344, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33288544

RESUMO

Granzyme B (GrB) is an immune protease implicated in the pathogenesis of several human diseases. In the current model of GrB activity, perforin determines whether the downstream actions of GrB occur intracellularly or extracellularly, producing apoptotic cytotoxicity or nonapoptotic effects, respectively. In the current study, we demonstrate the existence of a broad range of GrB-dependent signaling activities that 1) do not require perforin, 2) occur intracellularly, and 3) for which cell death is not the dominant outcome. In the absence of perforin, we show that GrB enzymatic activity still induces substoichiometric activation of caspases, which through nonlethal DNA damage response signals then leads to activity-associated phosphorylation of IFN regulatory factor-3. These findings illustrate an unexpected potential interface between GrB and innate immunity separate from the traditional role of GrB in perforin-dependent GrB-mediated apoptosis that could have mechanistic implications for human disease.


Assuntos
Fibroblastos/fisiologia , Granzimas/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Apoptose , Sobrevivência Celular , Células Cultivadas , Granzimas/genética , Células HEK293 , Humanos , Fator Regulador 3 de Interferon/genética , Mutação/genética , Perforina/metabolismo , Fosforilação , Proteólise , Transdução de Sinais
3.
Curr Cardiol Rep ; 25(5): 315-323, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36961658

RESUMO

PURPOSE OF REVIEW: Immune cells are emerging as central cellular components of the heart which communicate with cardiac resident cells during homeostasis, cardiac injury, and remodeling. These findings are contributing to the development and continuous expansion of the new field of cardio-immunology. We review the most recent literature on this topic and discuss ongoing and future efforts to advance this field forward. RECENT FINDINGS: Cell-fate mapping, strategy depleting, and reconstituting immune cells in pre-clinical models of cardiac disease, combined with the investigation of the human heart at the single cell level, are contributing immensely to our understanding of the complex intercellular communication between immune and non-immune cells in the heart. While the acute immune response is necessary to initiate inflammation and tissue repair post injury, it becomes detrimental when sustained over time and contributes to adverse cardiac remodeling and pathology. Understanding the specific functions of immune cells in the context of the cardiac environment will provide new opportunities for immunomodulation to induce or tune down inflammation as needed in heart disease.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência Cardíaca , Traumatismos Cardíacos , Humanos , Coração , Insuficiência Cardíaca/patologia , Traumatismos Cardíacos/patologia , Inflamação , Miocárdio/patologia , Remodelação Ventricular
4.
Respir Res ; 23(1): 168, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35751068

RESUMO

BACKGROUND: Studies of the respiratory tract microbiome primarily focus on airway and lung microbial diversity, but it is still unclear how these microbial communities may be affected by intubation and long periods in intensive care units (ICU), an aspect that today could aid in the understanding of COVID19 progression and disease severity. This study aimed to explore and characterize the endotracheal tube (ETT) microbiome by analyzing ETT-associated microbial communities. METHODS: This descriptive study was carried out on adult patients subjected to invasive mechanical ventilation from 2 to 21 days. ETT samples were obtained from 115 patients from ICU units in two hospitals. Bacteria isolated from endotracheal tubes belonging to the ESKAPE group were analyzed for biofilm formation using crystal violet quantification. Microbial profiles were obtained using Illumina sequencing of 16S rRNA gene. RESULTS: The ETT microbiome was mainly composed by the phyla Proteobacteria, Firmicutes and Bacteroidetes. Microbiome composition correlated with the ICU in which patients were hospitalized, while intubation time and diagnosis of ventilator-associated pneumonia (VAP) did not show any significant association. CONCLUSION: These results suggest that the ICU environment, or medical practices, could be a key to microbial colonization and have a direct influence on the ETT microbiomes of patients that require mechanical ventilation.


Assuntos
COVID-19 , Microbiota , Adulto , Biofilmes , Hospitais , Humanos , Intubação Intratraqueal/efeitos adversos , RNA Ribossômico 16S/genética , Respiração Artificial/efeitos adversos
5.
Environ Res ; 207: 112183, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637759

RESUMO

In urban ecosystems, microbes play a key role in maintaining major ecological functions that directly support human health and city life. However, the knowledge about the species composition and functions involved in urban environments is still limited, which is largely due to the lack of reference genomes in metagenomic studies comprises more than half of unclassified reads. Here we uncovered 732 novel bacterial species from 4728 samples collected from various common surface with the matching materials in the mass transit system across 60 cities by the MetaSUB Consortium. The number of novel species is significantly and positively correlated with the city population, and more novel species can be identified in the skin-associated samples. The in-depth analysis of the new gene catalog showed that the functional terms have a significant geographical distinguishability. Moreover, we revealed that more biosynthetic gene clusters (BGCs) can be found in novel species. The co-occurrence relationship between BGCs and genera and the geographical specificity of BGCs can also provide us more information for the synthesis pathways of natural products. Expanded the known urban microbiome diversity and suggested additional mechanisms for taxonomic and functional characterization of the urban microbiome. Considering the great impact of urban microbiomes on human life, our study can also facilitate the microbial interaction analysis between human and urban environment.


Assuntos
Metagenoma , Microbiota , Bactérias/genética , Humanos , Metagenômica , Interações Microbianas , Microbiota/genética
6.
Lupus ; 30(14): 2310-2317, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34874750

RESUMO

OBJECTIVE: Pregnant women with SLE have higher probabilities of maternal complications. SLE during pregnancy has alternating patterns of remission and flare-ups; however, most pregnant SLE patients tend to worsen with associated poor obstetric and perinatal outcomes. This study aimed to describe obstetric outcomes in pregnant women with SLE. METHODS: This retrospective study was performed between 2011 and 2020 at a highly complex referral health center in Cali, Colombia. Pregnant women with a diagnosis of SLE were included. Demographic, clinical, and laboratory features and obstetric and fetal outcomes, including intensive care unit (ICU) characteristics, were evaluated. RESULTS: Forty-eight pregnant women with SLE were included. The median age was 29 (25-33.7) years. The SLE diagnosis was made before pregnancy in 38 (79.1%) patients, with a median disease duration of 46 (12-84) months. Thirteen (27.1%) patients had lupus nephritis. Preterm labor (34, 70.8%), preeclampsia (25, 52%), and preterm rupture of membranes (10, 20.8%) were the most common obstetric complications. A relationship between a greater systemic lupus erythematosus pregnancy disease activity index (SLEPDAI) and the development of hypertensive disorders during pregnancy was established (preeclampsia = p < 0.0366; eclampsia = p < 0.0153). A relationship was identified between lupus nephritis (LN) and eclampsia (p < 0.01), preterm labor (p < 0.045), and placental abruption (p < 0.01). Seventeen (35.4%) patients required ICU admission; 52.9% of them were due to AID activity, 17.6% for cardiovascular damage, 11.7% for septic shock, and 5.8% for acute kidney failure. Fetal survival was 89.5% (N = 43/48). Among the live births, two (4.2%) newborns were diagnosed with neonatal lupus, and two (4.2%) were diagnosed with congenital heart block. One maternal death was registered due to preeclampsia and intraventricular hemorrhage. CONCLUSIONS: This study is the first to describe SLE during pregnancy in Colombia. SLE was the most prevalent AID in this cohort, and complications included preterm labor, preeclampsia, and postpartum hemorrhage. A higher SLEPDAI and lupus nephritis predicted adverse maternal outcomes.


Assuntos
Eclampsia , Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Trabalho de Parto Prematuro , Pré-Eclâmpsia , Complicações na Gravidez , Adulto , Colômbia/epidemiologia , Feminino , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Trabalho de Parto Prematuro/epidemiologia , Trabalho de Parto Prematuro/etiologia , Placenta , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos
7.
PLoS Med ; 17(9): e1003292, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32970670

RESUMO

BACKGROUND: Identifying stage II patients with colorectal cancer (CRC) at higher risk of progression is a clinical priority in order to optimize the advantages of adjuvant chemotherapy while avoiding unnecessary toxicity. Recently, the intensity and the quality of the host immune response in the tumor microenvironment have been reported to have an important role in tumorigenesis and an inverse association with tumor progression. This association is well established in microsatellite instable CRC. In this work, we aim to assess the usefulness of measures of T-cell infiltration as prognostic biomarkers in 640 stage II, CRC tumors, 582 of them confirmed microsatellite stable. METHODS AND FINDINGS: We measured both the quantity and clonality index of T cells by means of T-cell receptor (TCR) immunosequencing in a discovery dataset (95 patients with colon cancer diagnosed at stage II and microsatellite stable, median age 67, 30% women) and replicated the results in 3 additional series of stage II patients from 2 countries. Series 1 and 2 were recruited in Barcelona, Spain and included 112 fresh frozen (FF, median age 69, 44% women) and 163 formalin-fixed paraffin-embedded (FFPE, median age 67, 39% women) samples, respectively. Series 3 included 270 FFPE samples from patients recruited in Haifa, Northern Israel, as part of a large case-control study of CRC (median age 73, 46% women). Median follow-up time was 81.1 months. Cox regression models were fitted to evaluate the prognostic value of T-cell abundance and Simpson clonality of TCR variants adjusting by sex, age, tumor location, and stage (IIA and IIB). In the discovery dataset, higher TCR abundance was associated with better prognosis (hazard ratio [HR] for ≥Q1 = 0.25, 95% CI 0.10-0.63, P = 0.003). A functional analysis of gene expression on these tumors revealed enrichment in pathways related to immune response. Higher values of clonality index (lower diversity) were not associated with worse disease-free survival, though the HR for ≥Q3 was 2.32 (95% CI 0.90-5.97, P = 0.08). These results were replicated in an independent FF dataset (TCR abundance: HR = 0.30, 95% CI 0.12-0.72, P = 0.007; clonality: HR = 3.32, 95% CI 1.38-7.94, P = 0.007). Also, the association with prognosis was tested in 2 independent FFPE datasets. The same association was observed with TCR abundance (HR = 0.41, 95% CI 0.18-0.93, P = 0.03 and HR = 0.56, 95% CI 0.31-1, P = 0.042, respectively, for each FFPE dataset). However, the clonality index was associated with prognosis only in the FFPE dataset from Israel (HR = 2.45, 95% CI 1.39-4.32, P = 0.002). Finally, a combined analysis combining all microsatellite stable (MSS) samples demonstrated a clear prognosis value both for TCR abundance (HR = 0.39, 95% CI 0.26-0.57, P = 1.3e-06) and the clonality index (HR = 2.13, 95% CI 1.44-3.15, P = 0.0002). These associations were also observed when variables were considered continuous in the models (HR per log2 of TCR abundance = 0.85, 95% CI 0.78-0.93, P = 0.0002; HR per log2 or clonality index = 1.16, 95% CI 1.03-1.31, P = 0.016). LIMITATIONS: This is a retrospective study, and samples had been preserved with different methods. Validation series lack complete information about microsatellite instability (MSI) status and pathology assessment. The Molecular Epidemiology of Colorectal Cancer (MECC) study had information about overall survival instead of progression-free survival. CONCLUSION: Results from this study demonstrate that tumor lymphocytes, assessed by TCR repertoire quantification based on a sequencing method, are an independent prognostic factor in microsatellite stable stage II CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Repetições de Microssatélites/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Estudos de Casos e Controles , Quimioterapia Adjuvante , Neoplasias Colorretais/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Instabilidade de Microssatélites , Repetições de Microssatélites/imunologia , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espanha , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
8.
Clin Obstet Gynecol ; 63(2): 447-454, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32195682

RESUMO

One of the most common causes of obstetric morbidity and mortality is trauma in pregnancy. Several maternal physiological changes during pregnancy have a significant impact on the mechanism, presentation, and management of trauma in this population. It is crucial for health providers dealing with trauma to know and understand these differences between pregnant and nonpregnant patients. The obstetric trauma patient requires a multidisciplinary approach, including obstetrics, maternal fetal medicine, anesthesiology, surgery, and intensive care teams. The aim of this article is to review the most updated information on trauma during pregnancy.


Assuntos
Administração dos Cuidados ao Paciente/métodos , Complicações na Gravidez , Risco Ajustado/métodos , Ferimentos e Lesões , Feminino , Humanos , Equipe de Assistência ao Paciente/organização & administração , Gravidez/fisiologia , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/terapia , Prevalência , Serviços Preventivos de Saúde , Prognóstico , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
9.
Rev Gastroenterol Peru ; 40(2): 155-161, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32876632

RESUMO

INTRODUCTION: Fascioliasis is a disease caused by the parasite Fasciola hepatica, according to its clinical picture, it can be classified into two phases: acute and chronic, currently the diagnosis is made during the chronic phase, however, early detection would allow to provide an effective treatment and timely. Objetive: This study is carried out with the objective of evaluating the diagnostic validity of serological tests for the timely diagnosis of hepatic fascioliasis. MATERIALS AND METHODS: a systematic search of the literature was carried out in Embase, MedLine, Cochrane Library and LILACS. Study selection was performed by pairs of reviewers, diagnostic test studies were selected using: ELISA, indirect ELISA, rapid ELISA, Fas2 ELISA, Arco2 compared to sedimentation techniques for the diagnosis of hepatic fascioliasis in adults. The studies were evaluated using the QUADAS-2 tool. RESULTS: Seven studies were identified that answer the PICO question, with a total of 1,317 human serum samples, the tests reported high sensitivity and specificity, FhTA, ELISA, number of studies and participants identified, summary estimators with the corresponding confidence intervals / credibility, and the ranking of treatments. DISCUSSION: In general, the specificity of the serological tests was slightly higher than the sensitivity, there is evidence of moderate to low quality that reports their performance, however, the quality of the evidence and the heterogeneity between the studies do not allow determining its usefulness during the acute phase of the disease. More studies are needed in this regard. The studies were clinically heterogeneous between them.


Assuntos
Fasciolíase/sangue , Fasciolíase/diagnóstico , Humanos , Testes Sorológicos
10.
Emerg Infect Dis ; 25(4): 836-838, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30882330

RESUMO

We report Rickettsia parkeri and Candidatus Rickettsia andeanae in ticks of the Amblyomma maculatum group collected from dogs in Sonora, Mexico. Molecular characterization of these bacteria was accomplished by DNA amplification and sequence analysis of portions of the rickettsial genes gltA, htrA, ompA, and ompB.


Assuntos
Rickettsia , Infestações por Carrapato/epidemiologia , Carrapatos/microbiologia , Animais , Genes Bacterianos , Humanos , México/epidemiologia , Tipagem Molecular , Reação em Cadeia da Polimerase , Rickettsia/classificação , Rickettsia/genética , Rickettsia/isolamento & purificação , Análise de Sequência de DNA
11.
Curr Atheroscler Rep ; 21(9): 33, 2019 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-31230137

RESUMO

PURPOSE OF THE REVIEW: Maternal morbidity and mortality is rising in the USA, and maternal stroke is a major contributor. Here, we review the epidemiology, risk factors, and current recommendations for diagnosis and acute treatment of ischemic and hemorrhagic stroke during pregnancy and postpartum, focusing on recent evidence. RECENT FINDINGS: The incidence of maternal stroke has risen in recent years, possibly due to increasing rates of hypertensive disorders of pregnancy. The risk of maternal stroke is highest in the peripartum and early postpartum period. Preeclampsia is highly associated with reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome and is also associated with long-term increased risk of stroke and vascular dementia. Hypertensive disorders of pregnancy, migraine, and infections are risk factors for maternal stroke. Limited data suggest that thrombolytics and endovascular reperfusion therapy are safe and effective in pregnant women with ischemic stroke, but few data are available regarding safety of thrombolytics in the postpartum period. New consensus guidelines are now available to assist with management of ischemic and hemorrhagic stroke in pregnancy. Many gaps remain in our understanding of maternal stroke. While risk factors have been identified, there are no prediction tools to help identify which women might be at highest risk for postpartum stroke and require closer monitoring. The risk of recurrent maternal stroke has not been adequately quantified, limiting clinicians' ability to counsel patients. The complex pathophysiology of preeclampsia and its effects on the cerebral vasculature require further targeted study. An increased focus on the prevention, recognition, and optimal treatment of maternal stroke will be critical to reducing maternal morbidity and mortality.


Assuntos
Acidente Vascular Cerebral/epidemiologia , Adolescente , Adulto , Isquemia Encefálica/complicações , Feminino , Humanos , Incidência , Hemorragias Intracranianas/complicações , Mortalidade Materna , Síndrome da Leucoencefalopatia Posterior/complicações , Período Pós-Parto , Pré-Eclâmpsia , Gravidez , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Adulto Jovem
12.
Pediatr Dermatol ; 36(6): 961-962, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31468563

RESUMO

We describe a case of a 6-month-old female patient with a segmental, superficial, infantile hemangioma (IH) on the forehead being treated with propranolol 2 mg/kg/d for 5 months, who developed a symplastic hemangioma (SH) over the preexisting lesion, highlighting the need to consider SH in the differential diagnosis of vascular lesions arising over preexisting vascular anomalies in children.


Assuntos
Hemangioma/patologia , Segunda Neoplasia Primária/patologia , Neoplasias Cutâneas/patologia , Feminino , Hemangioma/tratamento farmacológico , Humanos , Lactente , Propranolol/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Vasodilatadores/uso terapêutico
13.
Antonie Van Leeuwenhoek ; 110(8): 1035-1051, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28523377

RESUMO

Microbial enrichments cultures are a useful strategy to speed up the search for enzymes that can be employed in industrial processes. Lipases have gained special attention because they show unique properties such as: broad substrate specificity, enantio- and regio-selectivity and stability in organic solvents. A major goal is to identify novel lipolytic enzymes from microorganisms living in cold extreme environments such as high Andean soils, of relevance to our study being their capability be used in industrial processes. Paramo and glacier soils from the Nevados National Park in Colombia were sampled and microbial communities enriched through a fed-batch fermentation using olive oil as an inductor substrate. After 15 days of enrichment under aerobic conditions, total DNA was extracted. Subsequently, metagenomic libraries were constructed in the cosmid vector pWEB-TNC™. After functional screening, twenty and eighteen lipolytic clones were obtained from Paramo and Glacier soil enrichments, respectively. Based on lipid hydrolysis halo dimensions, the clone (Gla1) from a glacier enrichment was selected. A gene related to lipolytic activity was subcloned to evaluate enzyme properties. Phylogenetic analysis of the identified gene showed that the encoded lipase belongs to the family GDSL from a Ralstonia-like species. Interestingly, the secreted enzyme exhibited stability at high temperature and alkaline conditions, specifically the preferred conditions at 80 °C and pH 9.0. Thus, with the identification of an enzyme with non-expected properties, in this study is shown the potential of extreme cold environments to be explored for new catalytic molecules, using current molecular biology techniques, with applications in industrial processes, which demand stability under harsh conditions.


Assuntos
Lipase/metabolismo , Microbiologia do Solo , Sequência de Aminoácidos , Bactérias/enzimologia , DNA , Filogenia , Alinhamento de Sequência , Solo , Especificidade por Substrato
14.
Appl Environ Microbiol ; 82(6): 1807-1817, 2016 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-26746719

RESUMO

Microbial populations residing in close contact with plants can be found in the rhizosphere, in the phyllosphere as epiphytes on the surface, or inside plants as endophytes. Here, we analyzed the microbiota associated with Espeletia plants, endemic to the Páramo environment of the Andes Mountains and a unique model for studying microbial populations and their adaptations to the adverse conditions of high-mountain neotropical ecosystems. Communities were analyzed using samples from the rhizosphere, necromass, and young and mature leaves, the last two analyzed separately as endophytes and epiphytes. The taxonomic composition determined by performing sequencing of the V5-V6 region of the 16S rRNA gene indicated differences among populations of the leaf phyllosphere, the necromass, and the rhizosphere, with predominance of some phyla but only few shared operational taxonomic units (OTUs). Functional profiles predicted on the basis of taxonomic affiliations differed from those obtained by GeoChip microarray analysis, which separated community functional capacities based on plant microenvironment. The identified metabolic pathways provided insight regarding microbial strategies for colonization and survival in these ecosystems. This study of novel plant phyllosphere microbiomes and their putative functional ecology is also the first step for future bioprospecting studies in search of enzymes, compounds, or microorganisms relevant to industry or for remediation efforts.


Assuntos
Archaea/isolamento & purificação , Asteraceae/microbiologia , Bactérias/isolamento & purificação , Biota , Redes e Vias Metabólicas/genética , Folhas de Planta/microbiologia , Archaea/classificação , Archaea/genética , Bactérias/classificação , Bactérias/genética , Colômbia , DNA Ribossômico/química , DNA Ribossômico/genética , Análise em Microsséries , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo
15.
Malar J ; 14: 233, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-26040274

RESUMO

BACKGROUND: The chemical treatment of Plasmodium falciparum for human infections is losing efficacy each year due to the rise of resistance. One possible strategy to find novel anti-malarial drugs is to access the largest reservoir of genomic biodiversity source on earth present in metagenomes of environmental microbial communities. METHODS: A bioluminescent P. falciparum parasite was used to quickly detect shifts in viability of microcultures grown in 96-well plates. A synthetic gene encoding the Dermaseptin 4 peptide was designed and cloned under tight transcriptional control in a large metagenomic insert context (30 kb) to serve as proof-of-principle for the screening platform. RESULTS: Decrease in parasite viability consistently correlated with bioluminescence emitted from parasite microcultures, after their exposure to bacterial extracts containing a plasmid or fosmid engineered to encode the Dermaseptin 4 anti-malarial peptide. CONCLUSIONS: Here, a new technical platform to access the anti-malarial potential in microbial environmental metagenomes has been developed.


Assuntos
Antimaláricos/farmacologia , Biblioteca Genômica , Testes de Sensibilidade Parasitária , Extratos Vegetais/farmacologia , Plantas/química , Plasmodium falciparum/efeitos dos fármacos , Biodiversidade , Malária Falciparum/tratamento farmacológico , Metagenoma , Plasmodium falciparum/genética
16.
Microbiology (Reading) ; 160(Pt 12): 2595-2606, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25261190

RESUMO

Klebsiella pneumoniae is an opportunistic pathogen important in hospital-acquired infections, which are complicated by the rise of drug-resistant strains and the capacity of cells to adhere to surfaces and form biofilms. In this work, we carried out an analysis of the genes in the K. pneumoniae yfiRNB operon, previously implicated in biofilm formation. The results indicated that in addition to the previously reported effect on type 3 fimbriae expression, this operon also affected biofilm formation due to changes in cellulose as part of the extracellular matrix. Deletion of yfiR resulted in enhanced biofilm formation and an altered colony phenotype indicative of cellulose overproduction when grown on solid indicator media. Extraction of polysaccharides and treatment with cellulase were consistent with the presence of cellulose in biofilms. The enhanced cellulose production did not, however, correlate with virulence as assessed using a Caenorhabditis elegans assay. In addition, cells bearing mutations in genes of the yfiRNB operon varied with respect to the WT control in terms of susceptibility to the antibiotics amikacin, ciprofloxacin, imipenem and meropenem. These results indicated that the yfiRNB operon is implicated in the production of exopolysaccharides that alter cell surface characteristics and the capacity to form biofilms--a phenotype that does not necessarily correlate with properties related with survival, such as resistance to antibiotics.


Assuntos
Antibacterianos/metabolismo , Biofilmes/crescimento & desenvolvimento , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/fisiologia , Óperon , Polissacarídeos Bacterianos/metabolismo , Animais , Caenorhabditis elegans/microbiologia , Celulose , Deleção de Genes , Genes Bacterianos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Virulência
17.
Int J Gynaecol Obstet ; 165(2): 453-461, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37846589

RESUMO

OBJECTIVES: To identify distinct subphenotypes of severe early-onset pre-eclampsia in Latin America and analyze biomarker and hemodynamic trends between subphenotypes after hospital admission. METHODS: A single-center prospective cohort study was conducted in Colombia. The latent class analysis identified subphenotypes using clinical variables, biomarkers, laboratory tests, and maternal hemodynamics. Class-defining variables were restricted to measurements at and 24 h after admission. Primary and secondary outcomes were severe maternal and perinatal complications. RESULTS: Among 49 patients, two subphenotypes were identified: Subphenotype 1 (34.7%) had a higher likelihood of an sFlt-1/PlGF ratio ≤ 38, maternal age > 35, and low probability of TPR > 1400, CO <8, and IUGR; Subphenotype 2 (65.3%) had a low likelihood of an sFlt-1/PlGF ratio < 38, maternal age > 35, and high probability of TPR > 1400, CO <8, and IUGR. At 24 h postadmission, 64.7% of subphenotype 1 patients changed to subphenotype 2, while 25% of subphenotype 2 patients were reclassified as subphenotype 1. Subphenotype 1 displayed significant changes in CO and TPR, while subphenotype 2 did not. Maternal complications were more prevalent in subphenotype 2, with an odds ratio of 5.3 (95% CI: 1.3-22.0; P = 0.02), but no significant differences in severe neonatal complications were observed. CONCLUSIONS: We identified two distinct subphenotypes in a Latin American cohort of patients with severe early-onset pre-eclampsia. Subphenotype 2, characterized by higher TPR, sFlt-1, and serum creatinine and lower CO and PlGF at admission, was associated with worse maternal outcomes and appeared less modifiable after in-hospital treatment.


Assuntos
Pré-Eclâmpsia , Gravidez , Feminino , Recém-Nascido , Humanos , América Latina , Estudos Prospectivos , Pré-Eclâmpsia/epidemiologia , Análise de Classes Latentes , Biomarcadores , Hospitais
18.
Microbiol Spectr ; 12(2): e0292823, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38189292

RESUMO

The genus Vibrio includes pathogenic bacteria able to cause disease in humans and aquatic organisms, leading to disease outbreaks and significant economic losses in the fishery industry. Despite much work on Vibrio in several marine organisms, no specific studies have been conducted on Anadara tuberculosa. This is a commercially important bivalve species, known as "piangua hembra," along Colombia's Pacific coast. Therefore, this study aimed to identify and characterize the genomes of Vibrio isolates obtained from A. tuberculosa. Bacterial isolates were obtained from 14 A. tuberculosa specimens collected from two locations along the Colombian Pacific coast, of which 17 strains were identified as Vibrio: V. parahaemolyticus (n = 12), V. alginolyticus (n = 3), V. fluvialis (n = 1), and V. natriegens (n = 1). Whole genome sequence of these isolates was done using Oxford Nanopore Technologies (ONT). The analysis revealed the presence of genes conferring resistance to ß-lactams, tetracyclines, chloramphenicol, and macrolides, indicating potential resistance to these antimicrobial agents. Genes associated with virulence were also found, suggesting the potential pathogenicity of these Vibrio isolates, as well as genes for Type III Secretion Systems (T3SS) and Type VI Secretion Systems (T6SS), which play crucial roles in delivering virulence factors and in interbacterial competition. This study represents the first genomic analysis of bacteria within A. tuberculosa, shedding light on Vibrio genetic factors and contributing to a comprehensive understanding of the pathogenic potential of these Vibrio isolates.IMPORTANCEThis study presents the first comprehensive report on the whole genome analysis of Vibrio isolates obtained from Anadara tuberculosa, a bivalve species of great significance for social and economic matters on the Pacific coast of Colombia. Research findings have significant implications for the field, as they provide crucial information on the genetic factors and possible pathogenicity of Vibrio isolates associated with A. tuberculosa. The identification of antimicrobial resistance genes and virulence factors within these isolates emphasizes the potential risks they pose to both human and animal health. Furthermore, the presence of genes associated with Type III and Type VI Secretion Systems suggests their critical role in virulence and interbacterial competition. Understanding the genetic factors that contribute to Vibrio bacterial virulence and survival strategies within their ecological niche is of utmost importance for the effective prevention and management of diseases in aquaculture practices.


Assuntos
Arcidae , Sistemas de Secreção Tipo VI , Vibrio parahaemolyticus , Animais , Humanos , Virulência/genética , Fatores de Virulência/genética , Antibacterianos
19.
J Med Entomol ; 61(3): 781-790, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38408183

RESUMO

The Pacific Coast tick (Dermacentor occidentalis Marx, 1892) is a frequently encountered and commonly reported human-biting tick species that has been recorded from most of California and parts of southwestern Oregon, southcentral Washington, and northwestern Mexico. Although previous investigators have surveyed populations of D. occidentalis for the presence of Rickettsia species across several regions of California, populations of this tick have not been surveyed heretofore for rickettsiae from Baja California, Oregon, or Washington. We evaluated 1,367 host-seeking, D. occidentalis adults collected from 2015 to 2022 by flagging vegetation at multiple sites in Baja California, Mexico, and Oregon and Washington, United States, using genus- and species-specific assays for spotted fever group rickettsiae. DNA of Rickettsia 364D, R. bellii, and R. tillamookensis was not detected in specimens from these regions. DNA of R. rhipicephali was detected in D. occidentalis specimens obtained from Ensenada Municipality in Baja California and southwestern Oregon, but not from Washington. All ompA sequences of R. rhipichephali that were amplified from individual ticks in southwestern Oregon were represented by a single genotype. DNA of the Ixodes pacificus rickettsial endosymbiont was amplified from specimens collected in southwestern Oregon and Klickitat County, Washington; to the best of our knowledge, this Rickettsia species has never been identified in D. occidentalis. Collectively, these data are consistent with a relatively recent introduction of Pacific Coast ticks in the northernmost extension of its recognized range.


Assuntos
Dermacentor , Rickettsia , Animais , Rickettsia/isolamento & purificação , Rickettsia/genética , Dermacentor/microbiologia , Washington , Oregon , Feminino , México , Masculino
20.
Sci China Life Sci ; 67(6): 1292-1301, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489008

RESUMO

Antimicrobial resistance (AMR) poses a critical threat to global health and development, with environmental factors-particularly in urban areas-contributing significantly to the spread of antibiotic resistance genes (ARGs). However, most research to date has been conducted at a local level, leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments. To address this issue, we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples, which were collected by the MetaSUB International Consortium involving diverse urban environments in 60 cities of 27 countries, utilizing a deep-learning based methodology. Our findings demonstrated the strong geographical specificity of urban environmental resistome, and their correlation with various local socioeconomic and medical conditions. We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters (BGCs) across different countries, and discovered that the urban environment represents a rich source of novel antibiotics. Our study provides a comprehensive overview of the global urban environmental resistome, and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.


Assuntos
Antibacterianos , Cidades , Humanos , Antibacterianos/farmacologia , Fatores Socioeconômicos , Metagenoma/genética , Farmacorresistência Bacteriana/genética , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Família Multigênica , Saúde Global
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA