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1.
PLoS One ; 19(9): e0300555, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39292730

RESUMEN

BACKGROUND: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated. OBJECTIVE: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0-19 years. METHODS: We conducted a national cross sectional serosurvey from June 1, 2022, to August 31, 2022, in children aged 0-19 years undergoing an anesthetic procedure at eight tertiary pediatric hospitals. Participant questionnaires were administered, and blood samples tested using the Roche Elecsys Anti-SARS-CoV-2 total spike and nucleocapsid antibody assays. Spike and nucleocapsid seroprevalence adjusted for geographic and socioeconomic imbalances in the participant sample compared to the Australian population was estimated using multilevel regression and poststratification within a Bayesian framework. RESULTS: Blood was collected from 2,046 participants (median age: 6.6 years). The overall adjusted seroprevalence of spike-antibody was 92.1% (95% credible interval (CrI) 91.0-93.3%) and nucleocapsid-antibody was 67.0% (95% CrI 64.6-69.3). In unvaccinated children spike and nucleocapsid antibody seroprevalences were 84.2% (95% CrI 81.9-86.5) and 67.1% (95%CrI 64.0-69.8), respectively. Seroprevalence was similar across geographic remoteness index and socioeconomic quintiles. Nucleocapsid antibody seroprevalence increased with age while the point seroprevalence of the spike antibody seroprevalence decreased in the first year of life and then increased to 97.8 (95% Crl 96.1-99.2) by 12-15 years of age. CONCLUSION: Most Australian children and adolescents aged 0-19 years, across all jurisdictions were infected with SARS-CoV-2 by August 2022, suggesting rapid and uniform spread across the population in a very short time period. High seropositivity in unvaccinated children informed COVID-19 vaccine recommendations in Australia.


Asunto(s)
Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Humanos , Niño , Preescolar , Australia/epidemiología , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/sangre , Adolescente , Estudios Seroepidemiológicos , Lactante , Estudios Transversales , Femenino , Masculino , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Recién Nacido , Adulto Joven , Glicoproteína de la Espiga del Coronavirus/inmunología
2.
Cell ; 187(19): 5195-5216, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39303686

RESUMEN

Microorganisms, including bacteria, archaea, viruses, fungi, and protists, are essential to life on Earth and the functioning of the biosphere. Here, we discuss the key roles of microorganisms in achieving the United Nations Sustainable Development Goals (SDGs), highlighting recent and emerging advances in microbial research and technology that can facilitate our transition toward a sustainable future. Given the central role of microorganisms in the biochemical processing of elements, synthesizing new materials, supporting human health, and facilitating life in managed and natural landscapes, microbial research and technologies are directly or indirectly relevant for achieving each of the SDGs. More importantly, the ubiquitous and global role of microbes means that they present new opportunities for synergistically accelerating progress toward multiple sustainability goals. By effectively managing microbial health, we can achieve solutions that address multiple sustainability targets ranging from climate and human health to food and energy production. Emerging international policy frameworks should reflect the vital importance of microorganisms in achieving a sustainable future.


Asunto(s)
Desarrollo Sostenible , Humanos , Naciones Unidas , Objetivos , Bacterias/metabolismo , Salud Global , Hongos/metabolismo
3.
Microbiome ; 12(1): 159, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39198891

RESUMEN

BACKGROUND: Prokaryotic microbes have impacted marine biogeochemical cycles for billions of years. Viruses also impact these cycles, through lysis, horizontal gene transfer, and encoding and expressing genes that contribute to metabolic reprogramming of prokaryotic cells. While this impact is difficult to quantify in nature, we hypothesized that it can be examined by surveying virus-encoded auxiliary metabolic genes (AMGs) and assessing their ecological context. RESULTS: We systematically developed a global ocean AMG catalog by integrating previously described and newly identified AMGs and then placed this catalog into ecological and metabolic contexts relevant to ocean biogeochemistry. From 7.6 terabases of Tara Oceans paired prokaryote- and virus-enriched metagenomic sequence data, we increased known ocean virus populations to 579,904 (up 16%). From these virus populations, we then conservatively identified 86,913 AMGs that grouped into 22,779 sequence-based gene clusters, 7248 (~ 32%) of which were not previously reported. Using our catalog and modeled data from mock communities, we estimate that ~ 19% of ocean virus populations carry at least one AMG. To understand AMGs in their metabolic context, we identified 340 metabolic pathways encoded by ocean microbes and showed that AMGs map to 128 of them. Furthermore, we identified metabolic "hot spots" targeted by virus AMGs, including nine pathways where most steps (≥ 0.75) were AMG-targeted (involved in carbohydrate, amino acid, fatty acid, and nucleotide metabolism), as well as other pathways where virus-encoded AMGs outnumbered cellular homologs (involved in lipid A phosphates, phosphatidylethanolamine, creatine biosynthesis, phosphoribosylamine-glycine ligase, and carbamoyl-phosphate synthase pathways). CONCLUSIONS: Together, this systematically curated, global ocean AMG catalog and analyses provide a valuable resource and foundational observations to understand the role of viruses in modulating global ocean metabolisms and their biogeochemical implications. Video Abstract.


Asunto(s)
Océanos y Mares , Agua de Mar , Agua de Mar/virología , Agua de Mar/microbiología , Metagenómica , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Virus/genética , Virus/clasificación , Virus/aislamiento & purificación , Células Procariotas/metabolismo , Células Procariotas/virología , Metagenoma , Redes y Vías Metabólicas/genética , Transferencia de Gen Horizontal , Fosfatidiletanolaminas/metabolismo
4.
Environ Microbiol ; 26(8): e16665, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39101434

RESUMEN

Soil microorganisms are pivotal in the global carbon cycle, but the viruses that affect them and their impact on ecosystems are less understood. In this study, we explored the diversity, dynamics, and ecology of soil viruses through 379 metagenomes collected annually from 2010 to 2017. These samples spanned the seasonally thawed active layer of a permafrost thaw gradient, which included palsa, bog, and fen habitats. We identified 5051 virus operational taxonomic units (vOTUs), doubling the known viruses for this site. These vOTUs were largely ephemeral within habitats, suggesting a turnover at the vOTU level from year to year. While the diversity varied by thaw stage and depth-related patterns were specific to each habitat, the virus communities did not significantly change over time. The abundance ratios of virus to host at the phylum level did not show consistent trends across the thaw gradient, depth, or time. To assess potential ecosystem impacts, we predicted hosts in silico and found viruses linked to microbial lineages involved in the carbon cycle, such as methanotrophy and methanogenesis. This included the identification of viruses of Candidatus Methanoflorens, a significant global methane contributor. We also detected a variety of potential auxiliary metabolic genes, including 24 carbon-degrading glycoside hydrolases, six of which are uniquely terrestrial. In conclusion, these long-term observations enhance our understanding of soil viruses in the context of climate-relevant processes and provide opportunities to explore their role in terrestrial carbon cycling.


Asunto(s)
Metagenoma , Hielos Perennes , Microbiología del Suelo , Virus , Hielos Perennes/microbiología , Hielos Perennes/virología , Virus/clasificación , Virus/genética , Virus/aislamiento & purificación , Ecosistema , Ciclo del Carbono , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación
5.
BMJ Open ; 14(8): e087560, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39209780

RESUMEN

INTRODUCTION: Substance use disorder (SUD) and problematic substance use are global public health concerns with significant multifaceted implications for physical health and psychosocial well-being. The impact of SUD extends beyond the individual to their family while imposing financial and social burdens on the community. Though family-centred interventions have shown promise in addressing SUD, their implementation and impact in low-income and middle-income countries (LMICs) remain underexplored. METHODS AND ANALYSIS: Per Joanna Briggs Institute's scoping review protocol, a systematic search strategy was employed across OVID Medline, Embase, PsycINFO, Web of Science-Core Collection, Global Health and CINAHL from 22 February 2024 to 26 February 2024, to identify relevant studies focused on family-centred interventions for SUD in LMIC, devoid of publication time and language constraints. Two independent reviewers will screen the titles, abstracts and full texts, with discrepancies resolved through discussion or third-party reviews. The extracted data charted in a structured form will be visualised by diagrams or tables, focusing on the feasibility and impact of family-centred interventions for SUD in LMIC. For qualitative studies, the findings will be synthesised and presented in thematic clusters, and for studies that report quantitative outcomes, specific health, including SUD and psychosocial, outcomes will be synthesised, aligning with the Population, Concept and Context framework. ETHICS AND DISSEMINATION: These data on substance use, psychosocial outcomes and perspectives of individuals with SUD and their families will be presented in narrative format, highlighting patterns and identifying research gaps. This review aims to synthesise the existing evidence on family-centred interventions for improving substance use and/or psychosocial outcomes in individuals with SUD in LMIC and seeks to inform future policy and practice. Ethics approval is not required for this scoping review, and modifications to the review protocol will be disclosed. Findings will be disseminated through conference proceedings and peer-reviewed publication.


Asunto(s)
Países en Desarrollo , Trastornos Relacionados con Sustancias , Humanos , Pobreza , Proyectos de Investigación , Literatura de Revisión como Asunto , Trastornos Relacionados con Sustancias/psicología , Trastornos Relacionados con Sustancias/terapia
6.
Nat Microbiol ; 9(6): 1454-1466, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38806673

RESUMEN

With rising global temperatures, permafrost carbon stores are vulnerable to microbial degradation. The enzyme latch theory states that polyphenols should accumulate in saturated peatlands due to diminished phenol oxidase activity, inhibiting resident microbes and promoting carbon stabilization. Pairing microbiome and geochemical measurements along a permafrost thaw-induced saturation gradient in Stordalen Mire, a model Arctic peatland, we confirmed a negative relationship between phenol oxidase expression and saturation but failed to support other trends predicted by the enzyme latch. To inventory alternative polyphenol removal strategies, we built CAMPER, a gene annotation tool leveraging polyphenol enzyme knowledge gleaned across microbial ecosystems. Applying CAMPER to genome-resolved metatranscriptomes, we identified genes for diverse polyphenol-active enzymes expressed by various microbial lineages under a range of redox conditions. This shifts the paradigm that polyphenols stabilize carbon in saturated soils and highlights the need to consider both oxic and anoxic polyphenol metabolisms to understand carbon cycling in changing ecosystems.


Asunto(s)
Ciclo del Carbono , Microbiota , Hielos Perennes , Polifenoles , Microbiología del Suelo , Polifenoles/metabolismo , Hielos Perennes/microbiología , Bacterias/metabolismo , Bacterias/genética , Bacterias/enzimología , Bacterias/clasificación , Carbono/metabolismo , Oxidación-Reducción , Regiones Árticas , Monofenol Monooxigenasa/metabolismo , Monofenol Monooxigenasa/genética , Suelo/química , Ecosistema
7.
Nat Commun ; 15(1): 4089, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744831

RESUMEN

Dominant microorganisms of the Sargasso Sea are key drivers of the global carbon cycle. However, associated viruses that shape microbial community structure and function are not well characterised. Here, we combined short and long read sequencing to survey Sargasso Sea phage communities in virus- and cellular fractions at viral maximum (80 m) and mesopelagic (200 m) depths. We identified 2,301 Sargasso Sea phage populations from 186 genera. Over half of the phage populations identified here lacked representation in global ocean viral metagenomes, whilst 177 of the 186 identified genera lacked representation in genomic databases of phage isolates. Viral fraction and cell-associated viral communities were decoupled, indicating viral turnover occurred across periods longer than the sampling period of three days. Inclusion of long-read data was critical for capturing the breadth of viral diversity. Phage isolates that infect the dominant bacterial taxa Prochlorococcus and Pelagibacter, usually regarded as cosmopolitan and abundant, were poorly represented.


Asunto(s)
Bacteriófagos , Metagenoma , Metagenómica , Océanos y Mares , Agua de Mar , Metagenómica/métodos , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Bacteriófagos/clasificación , Agua de Mar/virología , Agua de Mar/microbiología , Metagenoma/genética , Genoma Viral/genética , Filogenia , Prochlorococcus/virología , Prochlorococcus/genética , Microbiota/genética , Bacterias/genética , Bacterias/virología , Bacterias/clasificación , Bacterias/aislamiento & purificación
8.
J Immunother Cancer ; 12(5)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38821719

RESUMEN

BACKGROUND: To accelerate the translation of novel immunotherapeutic treatment approaches, the development of analytic methods to assess their efficacy at early in vitro stages is necessary. Using a droplet-based microfluidic platform, we have established a method for multiparameter quantifiable phenotypic and genomic observations of immunotherapies. Chimeric antigen receptor (CAR) natural killer (NK) cells are of increased interest in the current immunotherapy landscape and thus provide an optimal model for evaluating our novel methodology. METHODS: For this approach, NK cells transduced with a CD19 CAR were compared with non-transduced NK cells in their ability to kill a lymphoma cell line. Using our microfluidic platform, we were able to quantify the increase in cytotoxicity and synaptic contact formation of CAR NK cells over non-transduced NK cells. We then optimized our droplet sorter and successfully used it to separate NK cells based on target cell killing to perform transcriptomic analyses. RESULTS: Our data revealed expected improvement in cytotoxicity with the CD19 CAR but more importantly, provided unique insights into the factors involved in the cytotoxic mechanisms of CAR NK cells. This demonstrates a novel, improved system for accelerating the pre-clinical screening of future immunotherapy treatments. CONCLUSIONS: This study provides a new potential approach for enhanced early screening of immunotherapies to improve their development, with a highly relevant cell model to demonstrate. Additionally, our validation studies provided some potential insights into transcriptomic determinants influencing CAR NK cytotoxicity.


Asunto(s)
Células Asesinas Naturales , Receptores Quiméricos de Antígenos , Análisis de la Célula Individual , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Humanos , Análisis de la Célula Individual/métodos , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Inmunoterapia Adoptiva/métodos , Fenotipo , Citotoxicidad Inmunológica , Genotipo , Línea Celular Tumoral
9.
FEMS Microbiol Rev ; 48(3)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38678005

RESUMEN

Group B Streptococcus (GBS; also known as Streptococcus agalactiae) is an opportunistic bacterial pathogen that causes sepsis, meningitis, pneumonia, and skin and soft tissue infections in neonates and healthy or immunocompromised adults. GBS is well-adapted to survive in humans due to a plethora of virulence mechanisms that afford responses to support bacterial survival in dynamic host environments. These mechanisms and responses include counteraction of cell death from exposure to excess metal ions that can cause mismetallation and cytotoxicity, and strategies to combat molecules such as reactive oxygen and nitrogen species that are generated as part of innate host defence. Cytotoxicity from reactive molecules can stem from damage to proteins, DNA, and membrane lipids, potentially leading to bacterial cell death inside phagocytic cells or within extracellular spaces within the host. Deciphering the ways in which GBS responds to the stress of cytotoxic reactive molecules within the host will benefit the development of novel therapeutic and preventative strategies to manage the burden of GBS disease. This review summarizes knowledge of GBS carriage in humans and the mechanisms used by the bacteria to circumvent killing by these important elements of host immune defence: oxidative stress, nitrosative stress, and stress from metal ion intoxication/mismetallation.


Asunto(s)
Metales , Infecciones Estreptocócicas , Streptococcus agalactiae , Streptococcus agalactiae/fisiología , Streptococcus agalactiae/patogenicidad , Humanos , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/inmunología , Metales/metabolismo , Metales/toxicidad , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico , Virulencia , Infecciones Oportunistas/microbiología
10.
Nat Microbiol ; 9(5): 1340-1355, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38605174

RESUMEN

Although the significance of chemical modifications on RNA is acknowledged, the evolutionary benefits and specific roles in human immunodeficiency virus (HIV-1) replication remain elusive. Most studies have provided only population-averaged values of modifications for fragmented RNAs at low resolution and have relied on indirect analyses of phenotypic effects by perturbing host effectors. Here we analysed chemical modifications on HIV-1 RNAs at the full-length, single RNA level and nucleotide resolution using direct RNA sequencing methods. Our data reveal an unexpectedly simple HIV-1 modification landscape, highlighting three predominant N6-methyladenosine (m6A) modifications near the 3' end. More densely installed in spliced viral messenger RNAs than in genomic RNAs, these m6As play a crucial role in maintaining normal levels of HIV-1 RNA splicing and translation. HIV-1 generates diverse RNA subspecies with distinct m6A ensembles, and maintaining multiple of these m6As on its RNAs provides additional stability and resilience to HIV-1 replication, suggesting an unexplored viral RNA-level evolutionary strategy.


Asunto(s)
Adenosina , VIH-1 , ARN Viral , Replicación Viral , VIH-1/genética , ARN Viral/genética , ARN Viral/metabolismo , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Replicación Viral/genética , Empalme del ARN , Análisis de Secuencia de ARN/métodos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Infecciones por VIH/virología , Transcriptoma
11.
Microbiology (Reading) ; 170(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38656296

RESUMEN

Group B streptococcus (GBS) is a chain-forming commensal bacterium and opportunistic pathogen that resides in the gastrointestinal and genitourinary tract of healthy adults. GBS can cause various infections and related complications in pregnant and nonpregnant women, adults, and newborns. Investigations of the mechanisms by which GBS causes disease pathogenesis often utilize colony count assays to estimate bacterial population size in experimental models. In other streptococci, such as group A streptococcus and pneumococcus, variation in the chain length of the bacteria that can occur naturally or due to mutation can affect facets of pathogenesis, such as adherence to or colonization of a host. No studies have reported a relationship between GBS chain length and pathogenicity. Here, we used GBS strain 874391 and several derivative strains displaying longer chain-forming phenotypes (874391pgapC, 874391ΔcovR, 874391Δstp1) to assess the impact of chain length on bacterial population estimates based on the colony-forming unit (c.f.u.) assay. Disruption of GBS chains via bead beating or sonication in conjunction with fluorescence microscopy was used to compare chaining phenotypes pre- and post-disruption to detect long- and short-chain forms, respectively. We used a murine model of GBS colonization of the female reproductive tract to assess whether chaining may affect bacterial colonization dynamics in the host during chronic infection in vivo. Overall, we found that GBS exhibiting long-chain form can significantly affect population size estimates based on the colony count assay. Additionally, we found that the length of chaining of GBS can affect virulence in the reproductive tract colonization model. Collectively, these findings have implications for studies of GBS that utilize colony count assays to measure GBS populations and establish that chain length can affect infection dynamics and disease pathogenesis for this important opportunistic pathogen.


Asunto(s)
Infecciones Estreptocócicas , Streptococcus agalactiae , Factores de Virulencia , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidad , Femenino , Infecciones Estreptocócicas/microbiología , Ratones , Animales , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Humanos , Recuento de Colonia Microbiana , Virulencia , Modelos Animales de Enfermedad , Embarazo
12.
Chemistry ; 30(28): e202400268, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38472116

RESUMEN

Modern approaches in metallodrug research focus on compounds that bind protein targets rather than DNA. However, the identification of protein targets and binding sites is challenging. Using intact mass spectrometry and proteomics, we investigated the binding of the antimetastatic agent RAPTA-C to the model proteins ubiquitin, cytochrome c, lysozyme, and myoglobin. Binding to cytochrome c and lysozyme was negligible. However, ubiquitin bound up to three Ru moieties, two of which were localized at Met1 and His68 as [Ru(cym)], and [Ru(cym)] or [Ru(cym)(PTA)] adducts, respectively. Myoglobin bound up to four [Ru(cym)(PTA)] moieties and five sites were identified at His24, His36, His64, His81/82 and His113. Collision-induced unfolding (CIU) studies via ion-mobility mass spectrometry allowed measuring protein folding as a function of collisional activation. CIU of protein-RAPTA-C adducts showed binding of [Ru(cym)] to Met1 caused a significant compaction of ubiquitin, likely from N-terminal S-Ru-N chelation, while binding of [Ru(cym)(PTA)] to His residues of ubiquitin or myoglobin induced a smaller effect. Interestingly, the folded state of ubiquitin formed by His functionalization was more stable than Met1 metalation. The data suggests that selective metalation of amino acids at different positions on the protein impacts the conformation and potentially the biological activity of anticancer compounds.


Asunto(s)
Citocromos c , Muramidasa , Mioglobina , Pliegue de Proteína , Ubiquitina , Ubiquitina/química , Ubiquitina/metabolismo , Mioglobina/química , Mioglobina/metabolismo , Sitios de Unión , Citocromos c/química , Citocromos c/metabolismo , Muramidasa/química , Muramidasa/metabolismo , Unión Proteica , Rutenio/química , Complejos de Coordinación/química , Complejos de Coordinación/metabolismo
13.
ISME J ; 18(1)2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38552150

RESUMEN

Viruses impact microbial systems through killing hosts, horizontal gene transfer, and altering cellular metabolism, consequently impacting nutrient cycles. A virus-infected cell, a "virocell," is distinct from its uninfected sister cell as the virus commandeers cellular machinery to produce viruses rather than replicate cells. Problematically, virocell responses to the nutrient-limited conditions that abound in nature are poorly understood. Here we used a systems biology approach to investigate virocell metabolic reprogramming under nutrient limitation. Using transcriptomics, proteomics, lipidomics, and endo- and exo-metabolomics, we assessed how low phosphate (low-P) conditions impacted virocells of a marine Pseudoalteromonas host when independently infected by two unrelated phages (HP1 and HS2). With the combined stresses of infection and nutrient limitation, a set of nested responses were observed. First, low-P imposed common cellular responses on all cells (virocells and uninfected cells), including activating the canonical P-stress response, and decreasing transcription, translation, and extracellular organic matter consumption. Second, low-P imposed infection-specific responses (for both virocells), including enhancing nitrogen assimilation and fatty acid degradation, and decreasing extracellular lipid relative abundance. Third, low-P suggested virocell-specific strategies. Specifically, HS2-virocells regulated gene expression by increasing transcription and ribosomal protein production, whereas HP1-virocells accumulated host proteins, decreased extracellular peptide relative abundance, and invested in broader energy and resource acquisition. These results suggest that although environmental conditions shape metabolism in common ways regardless of infection, virocell-specific strategies exist to support viral replication during nutrient limitation, and a framework now exists for identifying metabolic strategies of nutrient-limited virocells in nature.


Asunto(s)
Bacteriófagos , Bacteriófagos/genética , Bacteriófagos/fisiología , Proteómica , Fosfatos/metabolismo , Metabolómica , Biología de Sistemas , Transcriptoma , Reprogramación Metabólica
14.
BMJ Case Rep ; 17(2)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38423579

RESUMEN

Aplastic anaemia is often associated with recent viral illnesses to include EBV and parvovirus along with certain medications such as anticonvulsants and sulfa containing antibiotics. We describe a case report of a female patient in her 70s who presented with pancytopenia after being treated with nitrofurantoin and ciprofloxacin for suspected urinary tract infection. She underwent an extensive workup to rule out alternative aetiologies of her pancytopenia to include a broad viral, autoimmune and malignancy evaluation which were unrevealing. Given her recent exposure to ciprofloxacin and nitrofurantoin and marrow recovery following removal of these agents, it was presumed that antibiotic exposure was the underlying cause of her aplastic anaemia.


Asunto(s)
Anemia Aplásica , Antibacterianos , Infecciones Urinarias , Femenino , Humanos , Anemia Aplásica/complicaciones , Anemia Aplásica/tratamiento farmacológico , Antibacterianos/efectos adversos , Ciprofloxacina/efectos adversos , Nitrofurantoína/efectos adversos , Pancitopenia/inducido químicamente , Pancitopenia/complicaciones , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/complicaciones , Anciano
15.
BMJ Open ; 14(2): e075569, 2024 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326269

RESUMEN

INTRODUCTION: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors. METHOD: Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses. ANALYSIS: Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model. ETHICS: National Mutual Acceptance ethical approval was obtained from the Sydney Children's Hospitals Network Human Research Ethics Committee (HREC). Local approvals were sought in each jurisdiction. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC. DISSEMINATION: Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Humanos , Animales , Niño , Encefalitis Japonesa/epidemiología , Encefalitis Japonesa/prevención & control , Estudios Transversales , Estudios Seroepidemiológicos , Teorema de Bayes , Australia/epidemiología , Anticuerpos Antivirales
16.
Nat Commun ; 15(1): 1441, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383596

RESUMEN

Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones.


Asunto(s)
Infecciones por Escherichia coli , Proteínas de Escherichia coli , Meningitis , Ratones , Animales , Ratas , Humanos , Virulencia/genética , Infecciones por Escherichia coli/microbiología , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Factores de Virulencia/genética , Filogenia
17.
J Cheminform ; 16(1): 15, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321500

RESUMEN

Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed as a result of the interactions between proteins and metal-based species. However, with increasing resolution, dataset size, and species complexity, the time required to identify adducts and the error-prone nature of manual assignment have become limiting factors in MS analysis. AdductHunter is a open-source web-based analysis tool that  automates the peak identification process using constraint integer optimization to find feasible combinations of protein and fragments, and dynamic time warping to calculate the dissimilarity between the theoretical isotope pattern of a species and its experimental isotope peak distribution. Empirical evaluation on a collection of 22 unique MS datasetsshows fast and accurate identification of protein-metal complex adducts in deconvoluted mass spectra.

18.
Emerg Top Life Sci ; 8(1): 45-56, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38362914

RESUMEN

Metal ions such as zinc and copper play important roles in host-microbe interactions and their availability can drastically affect the survival of pathogenic bacteria in a host niche. Mechanisms of metal homeostasis protect bacteria from starvation, or intoxication, defined as when metals are limiting, or in excess, respectively. In this mini-review, we summarise current knowledge on the mechanisms of resistance to metal stress in bacteria, focussing specifically on the homeostasis of cellular copper and zinc. This includes a summary of the factors that subvert metal stress in bacteria, which are independent of metal efflux systems, and commentary on the role of small molecules and metabolic systems as important mediators of metal resistance.


Asunto(s)
Cobre , Metales , Cobre/metabolismo , Metales/metabolismo , Homeostasis , Bacterias/metabolismo , Zinc/metabolismo
19.
Nat Commun ; 15(1): 1857, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424049

RESUMEN

Methane is a potent greenhouse gas contributing to global warming. Microorganisms largely drive the biogeochemical cycling of methane, yet little is known about viral contributions to methane metabolism (MM). We analyzed 982 publicly available metagenomes from host-associated and environmental habitats containing microbial MM genes, expanding the known MM auxiliary metabolic genes (AMGs) from three to 24, including seven genes exclusive to MM pathways. These AMGs are recovered on 911 viral contigs predicted to infect 14 prokaryotic phyla including Halobacteriota, Methanobacteriota, and Thermoproteota. Of those 24, most were encoded by viruses from rumen (16/24), with substantially fewer by viruses from environmental habitats (0-7/24). To search for additional MM AMGs from an environmental habitat, we generate metagenomes from methane-rich sediments in Vrana Lake, Croatia. Therein, we find diverse viral communities, with most viruses predicted to infect methanogens and methanotrophs and some encoding 13 AMGs that can modulate host metabolisms. However, none of these AMGs directly participate in MM pathways. Together these findings suggest that the extent to which viruses use AMGs to modulate host metabolic processes (e.g., MM) varies depending on the ecological properties of the habitat in which they dwell and is not always predictable by habitat biogeochemical properties.


Asunto(s)
Euryarchaeota , Virus , Animales , Metano/metabolismo , Ecosistema , Virus/genética , Metagenoma , Euryarchaeota/genética
20.
J Med Virol ; 96(1): e29407, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38240403

RESUMEN

In response to the emergence of the monkeypox virus (MPXV) in Australia in May 2022, we developed and evaluated indirect immunofluorescence assays (IFA) for MPXV and Vaccinia virus (VACV) IgG and IgM antibodies using serum samples from patients with nucleic acid amplification test (NAAT)-confirmed mpox and uninfected unvaccinated controls. Additionally, 47 healthcare workers receiving two doses of the third-generation smallpox vaccine Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) undertook serial serum collection to describe the serological response to vaccination. MPXV antibodies were detected in 16/18 individuals with NAAT-confirmed mpox (sensitivity 0.89, specificity 1.00), and VACV antibodies were detected in 28/29 individuals who received two doses of MVA-BN vaccine (sensitivity 0.97, specificity 1.00). Detectable antibody in subjects historically vaccinated with early-generation vaccines against smallpox was found in 7/7 subjects, at a median of 48 years following vaccination. MPXV NAAT-positive patients with serum samples collected within the first 14 days after rash onset had detectable IgG and IgM in 9/12 and 5/12 of patients, respectively, with maintenance of IgG and disappearance of IgM titers after 60 days. While specificity was high when testing unvaccinated and uninfected subjects, significant cross-reactivity between MPXV and VACV antibodies was observed.


Asunto(s)
Mpox , Vacuna contra Viruela , Vaccinia , Humanos , Virus Vaccinia , Mpox/epidemiología , Mpox/prevención & control , Formación de Anticuerpos , Australia/epidemiología , Anticuerpos Antivirales , Monkeypox virus , Inmunoglobulina M , Inmunoglobulina G , Vacunas Atenuadas
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