RESUMO
We report a novel Globicatella species causing extensive soft tissue infection in a man bitten by a stray domestic cat in the United Kingdom. We identified this bacterium by 16S rRNA gene sequencing, whole-genome sequencing, and biochemical profiling and determined antimicrobial drug susceptibility.
Assuntos
Aerococcaceae , Infecções por Bactérias Gram-Positivas , Infecções dos Tecidos Moles , Animais , Gatos , Infecções por Bactérias Gram-Positivas/microbiologia , RNA Ribossômico 16S/genética , Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/tratamento farmacológico , Aerococcaceae/genética , Bactérias/genéticaRESUMO
Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.
Assuntos
Escarlatina , Infecções Estreptocócicas , Humanos , Streptococcus pyogenes/genética , Escarlatina/epidemiologia , Alelos , Inglaterra/epidemiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Reação em Cadeia da Polimerase , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genéticaRESUMO
The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.
Assuntos
Infecções Estreptocócicas , Humanos , Análise por Conglomerados , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Surtos de Doenças/prevenção & controle , Inglaterra/epidemiologiaRESUMO
Increases in invasive group A streptococcal (iGAS) infection and associated deaths, particularly in children, above seasonally expected levels are being seen this season (772 notifications reported in weeks 37 to 48 in 2022) across England. Diagnoses of iGAS infection from lower respiratory tract specimens in children under 15 years increased to 28% in November 2022. Medical practitioners have been alerted to the exceptional increase in incidence, including unusual numbers of children presenting with pulmonary empyema.
Assuntos
Infecções Estreptocócicas , Streptococcus pyogenes , Criança , Humanos , Inglaterra/epidemiologia , Incidência , Estações do Ano , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Notificação de Doenças/estatística & dados numéricosRESUMO
BACKGROUND: The true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases. METHODS: Potentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7-89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists. RESULTS: Analysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days. CONCLUSIONS: Approximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.
Assuntos
Infecções Estreptocócicas , Streptococcus agalactiae , Hotspot de Doença , Estudos Epidemiológicos , Genômica , Humanos , Lactente , Irlanda/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/genética , Reino Unido/epidemiologiaRESUMO
Taste and odor compounds affect drinking water safety perception and may drive consumers to less secure water sources. Adsorption, using powered activated carbon, is the most common method to remove these compounds but greatly increases the amount of sludge generated. Another way of removing taste and odor compounds is to use filters with granular activated carbon (GAC) but little is still known on how to design them. In this work, the homogeneous surface diffusion model (HSDM) was used to model bench-scale kinetic and isotherm experiments and to simulate the removal of geosmin in a full-scale GAC filter. Geosmin adsorption isotherm was best described by the Freundlich model in all used carbons and film resistance (Kf) was more relevant to adsorption kinetics than pore diffusion (Ds). The simulation showed that in a filter with an empty bed contact time of 5 minutes and raw water with geosmin concentrations of 50, 75, and 100 ng.L-1, the effluent would exceed the trash-hold concentration (10 ng.L-1) in 98, 77, and 66 days, respectively, without considering biological removal.
Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Carvão Vegetal , NaftóisRESUMO
Background: Invasive Group B streptococcus (GBS) is a major cause of serious neonatal infection. Current strategies to reduce early-onset GBS disease have no impact on late-onset disease (LOD). Although GBS LOD is viewed as a sporadic event in the community, LOD arising within the neonatal intensive care unit (ICU) raises questions about mode of acquisition. Methods: Following a cluster of 4 GBS LOD cases, enhanced surveillance for all GBS LOD was undertaken over 2 years in the neonatal ICU supported by neonatal rectal screening. GBS isolates were serotyped and genome-sequenced. Results: Twelve late -onset invasive GBS episodes were identified (incidence 0.6/1000 live births). Genomic analysis revealed that 11/12 GBS isolates (92%) were linked to at least one other LOD isolate. Isolates from the first cluster were serotype V, resistant to macrolides and lincosamides, and sequencing confirmed isolates were indistinguishable, or distinguishable by only one SNP difference, from each other. Rectal carriage was rare. Prospective surveillance identified three further clusters of LOD due to serotypes Ia (3 cases), Ib (2 cases), and III (2 cases), that would not have been identified without surveillance and genome sequencing, leading to a re-evaluation of interventions required to prevent GBS LOD. Conclusion: Acquisition routes for LOD GBS in the neonatal ICU are poorly understood; cases may not necessarily be sporadic. Within this neonatal ICU, our data suggest that a single case of LOD GBS sepsis should be considered a potential nosocomial transmission event warranting prompt investigation, heightened infection prevention vigilance and action where required.
Assuntos
Unidades de Terapia Intensiva Neonatal , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/genética , Bacteriemia/epidemiologia , Análise por Conglomerados , Genômica , Humanos , Incidência , Recém-Nascido , Triagem Neonatal , Filogenia , Estudos Prospectivos , Fatores de Risco , Sorogrupo , Streptococcus agalactiae/isolamento & purificação , Reino Unido/epidemiologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: During a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, GAS) isolates from patients with SF with comparison to isolates from patients with invasive disease (iGAS) to test the hypotheses that the increase in SF was due to either the introduction of one or more new/emerging strains in the population in England or the transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF. Isolates were collected to provide geographical representation, for approximately 5% SF isolates from each region from 1st April 2014 to 18th June 2014. Contemporaneous iGAS isolates for which genomic data were available were included for comparison. Data were analysed in order to determine emm gene sequence type, phylogenetic lineage and genomic clade representation, the presence of known prophage elements and the presence of genes known to confer pathogenicity and resistance to antibiotics. RESULTS: 555 isolates were analysed, 303 from patients with SF and 252 from patients with iGAS. Isolates from patients with SF were of multiple distinct emm sequence types and phylogenetic lineages. Prior to data normalisation, emm3 was the predominant type (accounting for 42.9% of SF isolates, 130/303 95%CI 37.5-48.5; 14.7% higher than the percentage of emm3 isolates found in the iGAS isolates). Post-normalisation emm types, 4 and 12, were found to be over-represented in patients with SF versus iGAS (p < 0.001). A single gene, ssa, was over-represented in isolates from patients with SF. No single phage was found to be over represented in SF vs iGAS. However, a "meta-ssa" phage defined by the presence of :315.2, SPsP6, MGAS10750.3 or HK360ssa, was found to be over represented. The HKU360.vir phage was not detected yet the HKU360.ssa phage was present in 43/63 emm12 isolates but not found to be over-represented in isolates from patients with SF. CONCLUSIONS: There is no evidence that the increased number of SF cases was a strain-specific or known mobile element specific phenomenon, as the increase in SF cases was associated with multiple lineages of GAS.
Assuntos
Genoma Bacteriano , Genômica , Escarlatina/microbiologia , Streptococcus pyogenes/genética , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Bacteriófagos/genética , Proteínas de Transporte/genética , Análise por Conglomerados , Inglaterra/epidemiologia , Transferência Genética Horizontal , Genômica/métodos , Humanos , Tipagem de Sequências Multilocus , Filogenia , Vigilância da População , Escarlatina/epidemiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/virologiaRESUMO
Background: Like other streptococci, Streptococcus agalactiae typically has intrinsic low-level aminoglycoside resistance. High-level gentamicin resistance was seen in 2 of 1125 isolates collected in the BSAC Bacteraemia Surveillance Programme between 2001 and 2014. These organisms, both isolated in 2014, were characterized. Methods: Identifications were by latex agglutination, MICs by BSAC agar dilution and sequencing by Illumina methodology. Results: Gentamicin MICs were >1024 mg/L versus a species mode of 8 mg/L; both isolates also were unusually ciprofloxacin resistant with MICs of 64 mg/L versus a species mode of 1 mg/L. They were distinct by sequence, but both belonged to the ST19 clone, which occurs globally. Both had aac(6')-aph(2â³), carried by different transposons, explaining their gentamicin resistance, and had gyrA[81:S-L];parC[79:S-Y], accounting for ciprofloxacin resistance. Conclusions: These are the first multiresistant S. agalactiae with the bifunctional AAC(6')-APH(2â³) enzyme to be reported in the UK for >10 years. Despite belonging to the same clonal complex, the two isolates and their resistance transposons were distinct. Both retained full susceptibility to penicillin, but any penicillin/gentamicin synergy is likely to be lost.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/epidemiologia , Farmacorresistência Bacteriana/genética , Gentamicinas/farmacologia , Análise de Sequência de DNA/métodos , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/genética , Bacteriemia/microbiologia , Elementos de DNA Transponíveis , Monitoramento Epidemiológico , Genoma Bacteriano , Genômica/métodos , Humanos , Testes de Sensibilidade Microbiana/métodos , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificaçãoRESUMO
Invasive group A streptococcal infection has a 15% case fatality rate and a risk of secondary transmission. This retrospective study used two national data sources from England; enhanced surveillance (2009) and a case management system (2011-2013) to identify clusters of severe group A streptococcal disease. Twenty-four household pairs were identified. The median onset interval between cases was 2 days (range 0-28) with simultaneous onset in eight pairs. The attack rate during the 30 days after first exposure to a primary case was 4,520 per 100,000 person-years at risk (95% confidence interval (CI): 2,900-6,730) a 1,940 (95% CI: 1,240-2,880) fold elevation over the background incidence. The theoretical number needed to treat to prevent one secondary case using antibiotic prophylaxis was 271 overall (95% CI: 194-454), 50 for mother-neonate pairs (95% CI: 27-393) and 82 for couples aged 75 years and over (95% CI: 46-417). While a dramatically increased risk of infection was noted in all household contacts, increased risk was greatest for mother-neonate pairs and couples aged 75 and over, suggesting targeted prophylaxis could be considered. Offering prophylaxis is challenging due to the short time interval between cases emphasising the importance of immediate notification and assessment of contacts.
Assuntos
Antibioticoprofilaxia/métodos , Vigilância da População/métodos , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/transmissão , Streptococcus pyogenes/isolamento & purificação , Adolescente , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Inglaterra/epidemiologia , Características da Família , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/fisiologia , VirulênciaRESUMO
We report an outbreak of invasive and non-invasive disease due to an unusual type of Streptococcus pyogenes (group A Streptococcus, emm66) among a vulnerable, largely homeless population in southern England and Wales, detected in September 2016. Twenty-seven confirmed cases were subsequently identified between 5 January and 29 December 2016; 20 injected drugs and six reported problematic alcohol use. To date, we have ruled out drug-related vehicles of infection and identified few common risk factors.
Assuntos
Surtos de Doenças , Pessoas Mal Alojadas/estatística & dados numéricos , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/isolamento & purificação , Adulto , Distribuição por Idade , Notificação de Doenças , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus pyogenes/classificação , Streptococcus pyogenes/genética , Abuso de Substâncias por Via Intravenosa/epidemiologia , Populações Vulneráveis , País de Gales/epidemiologiaRESUMO
Single-strain outbreaks of Streptococcus pyogenes infections are common and often go undetected. In 2013, two clusters of invasive group A Streptococcus (iGAS) infection were identified in independent but closely located care homes in Oxfordshire, United Kingdom. Investigation included visits to each home, chart review, staff survey, microbiologic sampling, and genome sequencing. S. pyogenes emm type 1.0, the most common circulating type nationally, was identified from all cases yielding GAS isolates. A tailored whole-genome reference population comprising epidemiologically relevant contemporaneous isolates and published isolates was assembled. Data were analyzed independently using whole-genome multilocus sequencing and single-nucleotide polymorphism analyses. Six isolates from staff and residents of the homes formed a single cluster that was separated from the reference population by both analytical approaches. No further cases occurred after mass chemoprophylaxis and enhanced infection control. Our findings demonstrate the ability of 2 independent analytical approaches to enable robust conclusions from nonstandardized whole-genome analysis to support public health practice.
Assuntos
Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Alelos , Biologia Computacional/métodos , Farmacorresistência Bacteriana , Genoma Bacteriano , Genômica/métodos , Instalações de Saúde , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/transmissão , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/patogenicidade , Reino Unido/epidemiologia , Virulência/genética , Sequenciamento Completo do GenomaRESUMO
Recently, the consequences of diabetes on the central nervous system (CNS) have received great attention. However, the mechanisms by which hyperglycemia affects the central nervous system remain poorly understood. In addition, recent studies have shown that hyperglycemia induces oxidative damage in the adult rat brain. In this regard, no study has assessed oxidative stress as a possible mechanism that affects the brain normal function in neonatal hyperglycemic rats. Thus, the present study aimed to investigate whether neonatal hyperglycemia elicits oxidative stress in the brain of neonate rats subjected to a streptozotocin-induced neonatal hyperglycemia model (5-day-old rats). The activities of glucose-6-phosphate-dehydrogenase (G6PD), 6-phosphogluconate-dehydrogenase (6-PGD), NADPH oxidase (Nox), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), the production of superoxide anion, the thiobarbituric acid-reactive substances (TBA-RS), and the protein carbonyl content were measured. Neonatal hyperglycemic rats presented increased activities of G6PD, 6PGD, and Nox, which altogether may be responsible for the enhanced production of superoxide radical anion that was observed. The enhanced antioxidant enzyme activities (SOD, CAT, and GSHPx) that were observed in neonatal hyperglycemic rats, which may be caused by a rebound effect of oxidative stress, were not able to hinder the observed lipid peroxidation (TBA-RS) and protein damage in the brain. Consequently, these results suggest that oxidative stress could represent a mechanism that explains the harmful effects of neonatal hyperglycemia on the CNS.
Assuntos
Encéfalo/enzimologia , Encéfalo/patologia , Hiperglicemia/patologia , NADPH Oxidases/metabolismo , Estresse Oxidativo , Via de Pentose Fosfato , Animais , Animais Recém-Nascidos , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Carbonilação Proteica , Ratos Wistar , Superóxidos/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Pipecolic acid (PA) levels are increased in severe metabolic disorders of the central nervous system such as Zellweger syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and hyperlysinemia. The affected individuals present progressive neurological dysfunction, hypotonia and growth retardation. The mechanisms of brain damage of these disorders remain poorly understood. Since PA catabolism can produce H2O2 by oxidases, oxidative stress may be a possible mechanism involved in the pathophysiology of these diseases. Lipoic acid (LA) is considered an efficient antioxidant and has been shown to prevent oxidative stress in experimental models of many disorders of the neurologic system. Considering that to our knowledge no study investigated the role of PA on oxidative stress, in the present work we investigated the in vitro effects of PA on some oxidative stress parameters and evaluated the LA efficacy against possible pro-oxidant effects of PA in cerebral cortex of 14-day-old rats. The activities of catalase (CAT), glutathione peroxidase (GPx), glucose 6-phosphate dehydrogenase (G6PD), and glutathione S-transferase (GST) along with reduced glutathione (GSH) content were significantly decreased, while superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBA-RS) were significantly enhanced by PA. LA was able to prevent these effects by improving the activity of antioxidant enzymes, increasing GSH content and reducing TBA-RS. In contrast, glutathione reductase and 6-phosphogluconate dehydrogenase activities and sulfhydryl content were not affected. Taken together, it may be presumed that PA in vitro elicits oxidative stress and LA is able to prevent these effects.
Assuntos
Antioxidantes/farmacologia , Córtex Cerebral/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ácidos Pipecólicos/toxicidade , Ácido Tióctico/farmacologia , Animais , Catalase/análise , Córtex Cerebral/enzimologia , Feminino , Glutationa/análise , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos dos fármacos , Lisina/metabolismo , Masculino , Proteínas do Tecido Nervoso/análise , Oxirredutases/análise , Ratos , Ratos Wistar , Compostos de Sulfidrila/análise , Superóxido Dismutase/análise , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
This article aims to evaluate the adherence to antihypertensive treatment prevalence in the Brazilian population based on peer-reviewed studies which used instruments exclusively designed and/or adapted for this purpose. A systematic review with meta-analysis based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search was carried out in the BDENF, SciELO, Cuiden, PsycINFOe, CINAHL, Embase, LILACS, and MEDLINE databases, as well as the AgeLine, Google Scholar and ScienceDirect academic search engines. The protocol was registered with PROSPERO (CRD42021292689). Random effects models were used for a meta-analysis of the prevalence obtained from individual studies. A total of 104 studies were included in the meta-analysis on antihypertensive treatment in the Brazilian population, totaling 38,299 patients. The most used instrument was the four-item Morisky-Green Test (49.5%). The adherence prevalence estimated by the meta-analysis was 44.4% (95%CI: 39.12%-49.94%, I2 = 91.17, p < 0.001), showing high heterogeneity. The adherence to antihypertensive treatment prevalence found in national studies was unsatisfactory, demonstrating that this problem continues to be a major challenge.
O objetivo do artigo é avaliar a prevalência de adesão ao tratamento anti-hipertensivo na população brasileira, com base nos estudos revisados por pares, que utilizaram instrumentos elaborados e/ou adaptados exclusivamente para este fim. Revisão sistemática com meta-análise, baseada nas recomendações do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A busca foi realizada nas bases BDENF, SciELO, Cuiden, PsycINFOe, CINAHL, Embase, LILACS, MEDLINE, e nos buscadores acadêmicos AgeLine, Google Scholar e ScienceDirect. O protocolo foi registrado no PROSPERO (CRD42021292689). Modelos de efeitos aleatórios foram usados para meta-análise das prevalências obtidas dos estudos individuais. Incluíram-se 104 estudos na meta-análise sobre tratamento anti-hipertensivo na população brasileira, totalizando 38.299 pacientes. O instrumento mais utilizado foi o teste de Morisky-Green de quatro itens (49,5%). A prevalência de adesão estimada pela foi de 44,4% (IC95%: 39,12%-49,94%, I2 = 91,17, p < 0,001), apresentando alta heterogeneidade. A prevalência de adesão ao tratamento anti-hipertensivo encontrada nos estudos nacionais foi insatisfatória, demonstrando que essa problemática continua sendo um grande desafio.
Assuntos
Anti-Hipertensivos , Hipertensão , Adesão à Medicação , Brasil , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , PrevalênciaRESUMO
The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.
Assuntos
COVID-19 , Filogenia , Infecções Estreptocócicas , Streptococcus pyogenes , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade , Streptococcus pyogenes/isolamento & purificação , Reino Unido/epidemiologia , Humanos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , COVID-19/epidemiologia , Pandemias , Escarlatina/epidemiologia , Escarlatina/microbiologia , Mutação , Proteínas Repressoras/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Genoma Bacteriano , Europa (Continente)/epidemiologia , Proteínas de BactériasRESUMO
Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase which leads to accumulation of phenylalanine and its metabolites in tissues of patients with severe neurological involvement. Recently, many studies in animal models or patients have reported the role of oxidative stress in PKU. In the present work we studied the effect of lipoic acid against oxidative stress in rat brain provoked by an animal model of hyperphenylalaninemia (HPA), induced by repetitive injections of phenylalanine and α-methylphenylalanine (a phenylalanine hydroxylase inhibitor) for 7 days, on some oxidative stress parameters. Lipoic acid prevented alterations on catalase (CAT) and superoxide dismutase (SOD), and the oxidative damage of lipids, proteins, and DNA observed in HPA rats. In addition, lipoic acid diminished reactive species generation compared to HPA group which was positively correlated to SOD/CAT ratio. We also observed that in vitro Phe inhibited CAT activity while phenyllactic and phenylacetic acids stimulated superoxide dismutase activity. These results demonstrate the efficacy of lipoic acid to prevent oxidative stress induced by HPA model in rats. The possible benefits of lipoic acid administration to PKU patients should be considered.
Assuntos
Encéfalo/enzimologia , Catalase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenilcetonúrias/enzimologia , Fenilcetonúrias/patologia , Superóxido Dismutase/metabolismo , Ácido Tióctico/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Dano ao DNA , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fenilalanina/administração & dosagem , Fenilalanina/farmacologia , Fenilalanina Hidroxilase/antagonistas & inibidores , Fenilalanina Hidroxilase/metabolismo , Fenilcetonúrias/tratamento farmacológico , Ratos , Ratos Wistar , Ácido Tióctico/uso terapêuticoRESUMO
Streptococcus canis, a multi-host pathogen commonly isolated from dogs and cats, has been occasionally reported in severe cases of human infection. To address the gap in knowledge on its virulence and host tropism, we investigated S. canis genomic epidemiology and report the results of this analysis for the first time. We analysed 59 S. canis whole genome sequences originating from a variety of host species, comprising 39 newly sequenced isolates from UK sources, along with all (n=20) publicly available genomes. Antimicrobial resistance (AMR) phenotype was determined for all 39 available isolates. Genomes were screened for determinants of resistance and virulence. We created a core SNP phylogeny and compared strain clustering to multi-locus sequence typing (MLST) and S. canis M-like protein (SCM) typing. We investigated the dataset for signals of host adaptation using phylogenetic analysis, accessory genome clustering and pan-genome-wide association study analysis. A total of 23â% (9/39) of isolates exhibited phenotypic resistance to lincosamides, macrolides and/or tetracyclines. This was complemented by the identification of AMR-encoding genes in all genomes: tetracycline (tetO 14â%, 8/59; and tetM 7â%, 4/59) and lincosamide/macrolide (ermB, 7â%, 4/59). AMR was more common in human (36â%, 4/11) compared to companion animal (18â%, 5/28) isolates. We identified 19 virulence gene homologues, 14 of which were present in all strains analysed. In an S. canis strain isolated from a dog with otitis externa we identified a homologue of S. pyogenes superantigen SMEZ. The MLST and SCM typing schemes were found to be incapable of accurately representing core SNP-based genomic diversity of the S. canis population. No evidence of host adaptation was detected, suggesting the potential for inter-species transmission, including zoonotic transfer.
Assuntos
Doenças do Gato , Doenças do Cão , Animais , Humanos , Cães , Gatos , Tipagem de Sequências Multilocus , Filogenia , Estudo de Associação Genômica Ampla , Doenças do Cão/epidemiologia , Genômica , Antibacterianos/farmacologiaRESUMO
Introduction. Panton-Valentine leucocidin (PVL) toxin is a potential determinant of virulence associated with S. aureus infection.Gap Statement. The contribution of PVL to S. aureus pathogenicity remains unclear.Aim. To compare clinical outcomes in hospitalized patients with PVL-positive and PVL-negative community-acquired (CA) S. aureus bacteraemia.Methods. Three national datasets were combined to provide clinical and mortality data for patients with CA S. aureus blood culture isolates sent to the UK reference laboratory for PVL testing, August 2018 to August 2021. Multivariable logistic regression models were built for the effect of PVL positivity on 30 day all-cause mortality and 90 day readmission.Results. In 2191 cases of CA S. aureus bacteraemia, there was no association between PVL and mortality (adjusted odds ratio, aOR: 0·90, 95â% confidence interval, CI: 0·50-1·35, P=0·602) and no difference in median LOS (14 versus 15 days, P=0.169). PVL-positive cases had lower odds of readmission (aOR 0·74, CI 0·55-0.98, P=0·038). There was no evidence that MRSA status modified this effect (P=0·207).Conclusions. In patients with CA S. aureus bacteraemia PVL toxin detection was not associated with worse outcomes.
Assuntos
Bacteriemia , Infecções Comunitárias Adquiridas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Leucocidinas , Exotoxinas , VirulênciaRESUMO
Streptococcus pyogenes genotype emm1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An emm1 sublineage, M1UK, that produces increased levels of SpeA toxin was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1UK is now dominant in England. To more fully characterize M1UK, we undertook comparative transcriptomic and proteomic analyses of M1UK and contemporary non-M1UK emm1 strains (M1global). Just seven genes were differentially expressed by M1UK compared with contemporary M1global strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1UK (gldA, mipB/talC, pflD, and phosphotransferase system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UK strains have a stop codon in gldA. Deletion of gldA in M1global abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect. Phylogenetic analysis identified two intermediate emm1 sublineages in England comprising 13/27 (M113SNPs) and 23/27 SNPs (M123SNPs), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four phylogenetic emm1 groups highlighted sublineage-specific changes in carbohydrate metabolism, protein synthesis and protein processing; upregulation of SpeA was not observed in chemically defined medium. In rich broth, however, expression of SpeA was upregulated ~10-fold in both M123SNPs and M1UK sublineages, compared with M113SNPs and M1global. We conclude that stepwise accumulation of SNPs led to the emergence of M1UK. While increased expression of SpeA is a key indicator of M1UK and undoubtedly important, M1UK strains have outcompeted M123SNPs and other emm types that produce similar or more superantigen toxin. We speculate that an accumulation of adaptive SNPs has contributed to a wider fitness advantage in M1UK on an inherently successful emm1 streptococcal background.