27 research outputs found
Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome
Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Here, we show non-haemolytic enterotoxin (NHE) from the neglected human foodborne pathogen Bacillus cereus is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative transmembrane region, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunit B and subunit A, thus forming a tripartite lytic pore that is permissive to efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome
Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis
Background: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in
humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been
described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly
understood.
Methodology/Principal Findings: The sequencing of whole genomes of S. suis isolates provides opportunities to
investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same
lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was
used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for
which genome sequences are currently available. Accordingly, ,40% of the ,2 Mb genome is unique in comparison to
other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation;
virtually all of the genome is common to the S. suis strains. The only exceptions are three ,90 kb regions, present in the two
isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding
sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in
putative virulence and colonization factors.
Conclusions/Significance: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and
diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has
contributed to the evolution of drug resistance
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Transcriptional Landscape of the Prenatal Human Brain
Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development
Examining the Effectiveness of Climate Change Communication with Adolescents in Vietnam: The Role of Message Congruency
Climate change makes coastal communities more vulnerable to floods associated with storm surges and sea level rise, requiring both adaptation and mitigation measures. Moreover, proper understanding of flood risks and their potential impacts on climate change appears to be a communication challenge. In climate change communication, the effect of framing congruency on perception of risk, efficacy and behavioural intentions towards climate change adaptation and mitigation has received limited attention. Messages have not been congruent in framing risks associated with climate change. We define congruency as the coherent alignment of several aspects of message content. Messages are considered congruent when they provide recipients with consistent contents such as giving concrete and actionable advice, or by providing more abstract and general background information. This research focuses on climate change communication in fostering mitigation behaviours among adolescents in vulnerable locations in the global South. Based on Construal Level Theory, this paper investigates how message congruency affects the link between perceptions of climate change risk and efficacy and two predictors of behavioural change: perceived responsibility and mitigation intentions. We conducted an experiment to test the effect of congruent vs. incongruent risk communication among adolescents in highly vulnerable coastal communities in the Mekong Delta in Vietnam (N = 348). Multiple regression analysis found strong effects of congruency in message framing; when messages were congruent in the content, communicative interventions changed adolescents’ perceptions and attitudes toward climate change mitigation more consistently. This research contributes both theoretically and practically to risk communication among adolescents and toward climate change mitigation behaviour.Peer Reviewe
Drivers of flood and climate change risk perceptions and intention to adapt: an explorative survey in coastal and delta Vietnam
This article contributes to current research about determinants of climate change and flood risk perception, and intentions to take adaptive measures. We propose a research model that distinguishes between vulnerability and severity components of perceived risks, and adds perceived adaptive capacity as a third factor to predict the intention to take adaptive measures. We used this combined model as a conceptual lens for an explorative survey among 1086 residents of coastal and delta communities in Vietnam. Pairwise analyses revealed a significant association of flood and climate change risk perceptions with individual’s flood experience, climate change knowledge, frequency of community participation and socio-demographic factors. However, in multivariate analysis, the influence of most socio-demographic factors became weak or patchy. Flood experience was the most influential driver of flood-related risk perceptions but weak for climate change-related risk perceptions and behavioural intentions. Knowledge strongly increased the intention to adapt to flood and climate risks and the perceived vulnerability to and severity of climate change risks, but reduced the perceived capacity to adapt to climate risks. Frequency of community participation increased the perceived vulnerability and severity of climate change risks, the intention to adapt to both climate and flood risks and the perceived capacity to adapt to flood risks, but reduced the perceived capacity to adapt to climate risks. Our research confirms earlier findings that individuals’ knowledge, place-specific experience and social-cultural influences are key predictors of both flood and climate change risk perceptions and intentions to take adaptive measures. These factors should therefore receive ample attention in climate risk communication.</p
Predominant Bacteria Detected from the Middle Ear Fluid of Children Experiencing Otitis Media: A Systematic Review
<div><p>Background</p><p>Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention.</p><p>Methods</p><p>A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases.</p><p>Results</p><p>This review confirmed that <i>Streptococcus pneumoniae</i> and <i>Haemophilus influenzae</i>, remain the predominant bacterial pathogens, with <i>S</i>. <i>pneumoniae</i> the predominant bacterium in the majority reports from AOM patients. In contrast, <i>H</i>. <i>influenzae</i> was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of <i>S</i>. <i>pneumoniae</i> and <i>H</i>. <i>influenzae</i> 3.2 fold compared to culture, whilst <i>Moraxella catarrhalis</i> was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of <i>S</i>. <i>pneumoniae</i> and <i>H</i>. <i>influenzae</i> over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine.</p><p>Conclusions</p><p>Globally, <i>S</i>. <i>pneumoniae and H</i>. <i>influenzae</i> remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations.</p></div
Comparison of otopathogen detection in MEF using culture and PCR.
<p>Comparison of otopathogen detection in MEF using culture and PCR.</p
<i>S</i>. <i>pneumoniae</i>, <i>H</i>. <i>influenzae</i> and <i>M</i>. <i>catarrhalis</i> detected from MEF of patients with RAOM/AOMTF.
<p><i>S</i>. <i>pneumoniae</i>, <i>H</i>. <i>influenzae</i> and <i>M</i>. <i>catarrhalis</i> detected from MEF of patients with RAOM/AOMTF.</p
<i>S</i>. <i>pneumoniae</i>, <i>H</i>. <i>influenzae</i> and <i>M</i>. <i>catarrhalis</i> detected from MEF of patients with OME/COME.
<p><i>S</i>. <i>pneumoniae</i>, <i>H</i>. <i>influenzae</i> and <i>M</i>. <i>catarrhalis</i> detected from MEF of patients with OME/COME.</p