Enhanced nasopharyngeal infection and shedding associated with an epidemic lineage of emm3 group A Streptococcus

Background: A group A Streptococcus (GAS) lineage of genotype emm3, sequence type 15 (ST15) was associated with a six month upsurge in invasive GAS disease in the UK. The epidemic lineage (Lineage C) had lost two typical emm3 prophages, Φ315.1 and Φ315.2 associated with the superantigen ssa, but gained a different prophage (ΦUK-M3.1) associated with a different superantigen, speC and a DNAse spd1. Methods and Results: The presence of speC and spd1 in Lineage C ST15 strains enhanced both in vitro mitogenic and DNAse activities over non-Lineage C ST15 strains. Invasive disease models in Galleria mellonella and SPEC-sensitive transgenic mice, revealed no difference in overall invasiveness of Lineage C ST15 strains compared to non-Lineage C ST15 strains, consistent with clinical and epidemiological analysis. Lineage C strains did however markedly prolong murine nasal infection with enhanced nasal and airborne shedding compared to non-Lineage C strains. Deletion of speC or spd1 in two Lineage C strains identified a possible role for spd1 in airborne shedding from the murine nasopharynx. Conclusions: Nasopharyngeal infection and shedding of Lineage C strains was enhanced compared to nonLineage C strains and this was, in part, mediated by the gain of the DNase spd1 through prophage acquisition

Turner et al. Reply to "Emergence of the Same Successful Clade among Distinct Populations of emm89 Streptococcus pyogenes in Multiple Geographic Regions"

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The Emergence of Successful Streptococcus pyogenes Lineages through Convergent Pathways of Capsule Loss and Recombination Directing High Toxin Expression.

Gene transfer and homologous recombination in Streptococcus pyogenes has the potential to trigger the emergence of pandemic lineages, as exemplified by lineages of emm1 and emm89 that emerged in the 1980s and 2000s, respectively. Although near-identical replacement gene transfer events in the nga (NADase) and slo (streptolysin O) loci conferring high expression of these toxins underpinned the success of these lineages, extension to other emm genotype lineages is unreported. The emergent emm89 lineage was characterized by five regions of homologous recombination additional to nga-slo, including complete loss of the hyaluronic acid capsule synthesis locus hasABC, a genetic trait replicated in two other leading emm types and recapitulated by other emm types by inactivating mutations. We hypothesized that other leading genotypes may have undergone similar recombination events. We analyzed a longitudinal data set of genomes from 344 clinical invasive disease isolates representative of locations across England, dating from 2001 to 2011, and an international collection of S. pyogenes genomes representing 54 different genotypes and found frequent evidence of recombination events at the nga-slo locus predicted to confer higher toxin genotype. We identified multiple associations between recombination at this locus and inactivating mutations within hasAB, suggesting convergent evolutionary pathways in successful genotypes. This included common genotypes emm28 and emm87. The combination of no or low capsule and high expression of nga and slo may underpin the success of many emergent S. pyogenes lineages of different genotypes, triggering new pandemics, and could change the way S. pyogenes causes disease.IMPORTANCE Streptococcus pyogenes is a genetically diverse pathogen, with over 200 different genotypes defined by emm typing, but only a minority of these genotypes are responsible for the majority of human infection in high-income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that conferred increased expression. Here, we found that recombination of this locus and promoter has occurred in other diverse genotypes, events that may allow these genotypes to expand in the population. We identified an association between the loss of hyaluronic acid capsule synthesis and high toxin expression, which we propose may be associated with an adaptive advantage. As S. pyogenes pathogenesis depends both on capsule and toxin production, new variants with altered expression may result in abrupt changes in the molecular epidemiology of this pathogen in the human population over time

Emergence of a New Highly Successful Acapsular Group A Streptococcus Clade of Genotype emm89 in the United Kingdom

UNLABELLED: Group A Streptococcus (GAS) genotype emm89 is increasingly recognized as a leading cause of disease worldwide, yet factors that underlie the success of this emm type are unknown. Surveillance identified a sustained nationwide increase in emm89 invasive GAS disease in the United Kingdom, prompting longitudinal investigation of this genotype. Whole-genome sequencing revealed a recent dramatic shift in the emm89 population with the emergence of a new clade that increased to dominance over previous emm89 variants. Temporal analysis indicated that the clade arose in the early 1990s but abruptly increased in prevalence in 2008, coinciding with an increased incidence of emm89 infections. Although standard variable typing regions (emm subtype, tee type, sof type, and multilocus sequence typing [MLST]) remained unchanged, uniquely the emergent clade had undergone six distinct regions of homologous recombination across the genome compared to the rest of the sequenced emm89 population. Two of these regions affected known virulence factors, the hyaluronic acid capsule and the toxins NADase and streptolysin O. Unexpectedly, and in contrast to the rest of the sequenced emm89 population, the emergent clade-associated strains were genetically acapsular, rendering them unable to produce the hyaluronic acid capsule. The emergent clade-associated strains had also acquired an NADase/streptolysin O locus nearly identical to that found in emm12 and modern emm1 strains but different from the rest of the sequenced emm89 population. The emergent clade-associated strains had enhanced expression of NADase and streptolysin O. The genome remodeling in the new clade variant and the resultant altered phenotype appear to have conferred a selective advantage over other emm89 variants and may explain the changes observed in emm89 GAS epidemiology. IMPORTANCE: Sudden upsurges or epidemic waves are common features of group A streptococcal disease. Although the mechanisms behind such changes are largely unknown, they are often associated with an expansion of a single genotype within the population. Using whole-genome sequencing, we investigated a nationwide increase in invasive disease caused by the genotype emm89 in the United Kingdom. We identified a new clade variant that had recently emerged in the emm89 population after having undergone several core genomic recombination-related changes, two of which affected known virulence factors. An unusual finding of the new variant was the loss of the hyaluronic acid capsule, previously thought to be essential for causing invasive disease. A further genomic adaptation in the NADase/streptolysin O locus resulted in enhanced production of these toxins. Recombination-related genome remodeling is clearly an important mechanism in group A Streptococcus that can give rise to more successful and potentially more pathogenic variants

Evaluating the use of dominant microbial consumers (testate amoebae) as indicators of blanket peatland restoration

Peatlands represent globally-important ecosystems and carbon stores. However, large areas of peatland have been drained for agriculture, or peat has been harvested for use as fuel or in horticulture. Increasingly, these landscapes are being restored through ditch blocking and rewetting primarily to improve biodiversity and promote peat accumulation. To date we have little knowledge of how these interventions influence the microbial communities in peatlands. We compared the responses of dominant microbial consumers (testate amoebae) to drainage ditch restoration relative to unblocked ditches in a UK upland blanket peatland (Migneint, North Wales). Two techniques were used for restoration: (i) dammed ditches with re-profiling; and (ii) dammed ditches with pools of open water behind each dam. Testate communities in the inter-ditch areas changed markedly over time and between treatments illustrating the potential of this group of organisms as indicators of blanket peatland restoration status. However, the responses of testate amoebae to peat rewetting associated with restoration were partially obscured by inter-annual variability in weather conditions through the course of the experiment. Although there was considerable variability in the response of testate amoebae communities to peatland drain blocking, there were clearly more pronounced changes in samples from the dammed and reprofiled treatments including an increase in diversity, and the appearance of unambiguous wet-indicator species in relatively high abundances (including Amphitrema stenostoma, Archerella flavum, Arcella discoides type, Difflugia bacillifera and Difflugia bacillarium). This reflects a shift towards overall wetter conditions across the site and the creation of new habitats. However, water-table was not a significant control on testate amoebae in this case, suggesting a poor relationship between water table and surface moisture in this sloping blanket peatland. Our findings highlight the potential of testate amoebae as bioindicators of peatland restoration success; however, there is a need for caution as mechanisms driving change in the microbial communities may be more complex than first assumed. Several factors need to be taken into account when implementing biomonitoring studies in peatlands including: (i) the natural variability of the peatland ecosystem under changing weather conditions; (ii) any disturbance connected with the restoration procedures; and (iii) the timescales over which the ecosystem responds to the management intervention. Our results also suggest an indicator species approach based on population dynamics may be more appropriate for biomonitoring peatland restoration than examining changes at the community level

Testing peatland water-table depth transfer functions using high-resolution hydrological monitoring data

Transfer functions are now commonly used to reconstruct past environmental variability from palaeoecological data. However, such approaches need to be critically appraised. Testate amoeba-based transfer functions are an established method for the quantitative reconstruction of past water-table variations in peatlands, and have been applied to research questions in palaeoclimatology, peatland ecohydrology and archaeology. We analysed automatically-logged peatland water-table data from dipwells located in England, Wales and Finland and a suite of three year, one year and summer water-table statistics were calculated from each location. Surface moss samples were extracted from beside each dipwell and the testate amoebae community composition was determined. Two published transfer functions were applied to the testate-amoeba data for prediction of water-table depth (England and Europe). Our results show that estimated water-table depths based on the testate amoeba community reflect directional changes, but that they are poor representations of the real mean or median water-table magnitudes for the study sites. We suggest that although testate amoeba-based reconstructions can be used to identify past shifts in peat hydrology, they cannot currently be used to establish precise hydrological baselines such as those needed to inform management and restoration of peatlands. One approach to avoid confusion with contemporary water-table determinations is to use residuals or standardised values for peatland water-table reconstructions. We contend that our test of transfer functions against independent instrumental data sets may be more powerful than relying on statistical testing alone

Impact of negative and positive CO2 emissions on global warming metrics using an ensemble of Earth system model simulations

The benefits of implementing negative emission technologies in the global warming response to cumulative carbon emissions until the year 2420 are assessed following the shared socioeconomic pathway (SSP) 1-2.6, the sustainable development scenario, with a comprehensive set of intermediate-complexity Earth system model integrations. Model integrations include 86 different model realisations covering a wide range of plausible climate states. The global warming response is assessed in terms of two key climate metrics: the effective transient climate response to cumulative CO2 emissions (eTCRE), measuring the surface warming response to cumulative carbon emissions and associated non-CO2 forcing, and the effective zero emissions commitment (eZEC), measuring the extent of any continued warming after net-zero CO2 emissions are reached. The transient climate response to cumulative CO2 emissions (TCRE) is estimated as 2.2 K EgC−1 (median value) with a 10 %–90 % range of 1.75 to 3.13 K EgC−1 in 2100, approximated from the eTCRE by removing the contribution of non-CO2 forcing. During the positive emission phase, the eTCRE decreases from 2.71 (2.0 to 3.65) to 2.61 (1.91 to 3.62) K EgC−1 due to a weakening in the dependence of radiative forcing on atmospheric carbon, which is partly opposed by an increasing fraction of the radiative forcing warming the surface as the ocean stratifies. During the net negative and zero emission phases, a progressive reduction in the eTCRE to 2.0 (1.39 to 2.96) K EgC−1 is driven by the reducing airborne fraction as atmospheric CO2 is drawn down mainly by the ocean. The model uncertainty in the slopes of warming versus cumulative CO2 emissions varies from being controlled by the radiative feedback parameter during positive emissions to being affected by carbon-cycle parameters during net negative emissions, consistent with the drivers of uncertainty diagnosed from the coefficient of variation of the contributions in the eTCRE framework. The continued warming after CO2 emissions cease and remain at zero gives a model mean eZEC of −0.03 K after 25 years, which decreases in time to −0.21 K at 90 years after emissions cease. However, there is a spread in the ensemble with a temperature overshoot occurring in 20 % of the ensemble members at 25 years after cessation of emissions. If net negative emissions are included, there is a reduction in atmospheric CO2 and there is a decrease in temperature overshoot so that the eZEC is positive in only 5 % of the ensemble members. Hence, incorporating negative emissions enhances the ability to meet climate targets and avoid risk of continued warming after net zero is reached

An X-ray review of MS1054-0321: hot or not?

XMM-Newton observations are presented for the z=0.83 cluster of galaxies MS1054-0321, the highest redshift cluster in the Einstein Extended Medium Sensitivity Survey (EMSS). The temperature inferred by the XMM-Newton data, T=7.2 (+0.7, -0.6) keV, is much lower than the temperature previously reported from ASCA data, T=12.3 (+3.1, -2.2) keV (Donahue et al. 1998), and a little lower than the Chandra temperature, T=10.4(+1.7, -1.5) keV, determined by Jeltema et al. 2001. The discrepancy between the newly derived temperature and the previously derived temperatures is discussed in detail. If one allows the column density to be a free parameter, then the best fit temperature becomes T=8.6 (+1.2, -1.1) keV, and the best fit column density becomes N_(H)=1.33 (+0.15 -0.14) x 10^20 atoms/cm^2. The iron line is well detected in the XMM-Newton spectrum with a value for the abundance of Z=0.33 (+0.19 -0.18) Zsol, in very good agreement with previous determinations. The derived XMM X-ray luminosity for the overall cluster in the 2-10 keV energy band is L_X=(3.81 +/- 0.19) x 10^44 h^-2 erg s^-1 while the bolometric luminosity is L_BOL=(8.05+/-0.40) x 10^44 h^-2 erg s^-1. The XMM-Newton data confirm the substructure in the cluster X-ray morphology already seen by ROSAT and in much more detail by Chandra. The central weak lensing clump is coincident with the main cluster component and has a temperature T=8.1 (+1.3, -1.2) keV. The western weak lensing clump coincides with the western X-ray component which is much cooler with a temperature T=5.6 (+0.8, -0.6)$ keV. Given the newly determined temperature, MS1054-0321 is no longer amongst the hottest clusters known.Comment: To appear in the A&A main Journal, 13 pages including 3 postscript figures and 4 tables. Figs. 1, 4, 5 and 7 are too large and are not given here. The whole paper as pdf file is posted at http://www.ira.cnr.it/~gioia/PUB/publications.htm