A point mutation in cpsE renders Streptococcus pneumoniae nonencapsulated and enhances its growth, adherence and competence.

BACKGROUND: The polysaccharide capsule is a major virulence factor of the important human pathogen Streptococcus pneumoniae. However, S. pneumoniae strains lacking capsule do occur. RESULTS: Here, we report a nasopharyngeal isolate of Streptococcus pneumoniae composed of a mixture of two phenotypes; one encapsulated (serotype 18C) and the other nonencapsulated, determined by serotyping, electron microscopy and fluorescence isothiocyanate dextran exclusion assay.By whole genome sequencing, we demonstrated that the phenotypes differ by a single nucleotide base pair in capsular gene cpsE (C to G change at gene position 1135) predicted to result in amino acid change from arginine to glycine at position 379, located in the cytoplasmic, enzymatically active, region of this transmembrane protein. This SNP is responsible for loss of capsule production as the phenotype is transferred with the capsule operon. The nonencapsulated variant is superior in growth in vitro and is also 117-fold more adherent to and more invasive into Detroit 562 human epithelial cells than the encapsulated variant.Expression of six competence pathway genes and one competence-associated gene was 11 to 34-fold higher in the nonencapsulated variant than the encapsulated and transformation frequency was 3.7-fold greater. CONCLUSIONS: We identified a new single point mutation in capsule gene cpsE of a clinical S. pneumoniae serotype 18C isolate sufficient to cause loss of capsule expression resulting in the co-existence of the encapsulated and nonencapsulated phenotype. The mutation caused phenotypic changes in growth, adherence to epithelial cells and transformability. Mutation in capsule gene cpsE may be a way for S. pneumoniae to lose its capsule and increase its colonization potential

Red Blood Cell Transfusion and Mortality in Trauma Patients:Risk-Stratified Analysis of an Observational Study

Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death

Mortality with red blood cell transfusion by risk category and geographical region.

<p>Interaction between RBC transfusion and predicted risk of death on the OR, <i>p<</i>0.0001 for each continent grouping.</p>a<p>OR for RBC transfusion versus no RBC transfusion. Risk group determined according to model published in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001664#pmed.1001664-Perel1" target="_blank">[10]</a>.</p

Mortality by category of predicted risk of death and red blood cell transfusion.

<p>Interaction between RBC transfusion and predicted risk of death on the OR, <i>p<</i>0.0001 (chi-square <i> = </i>227 with one degree of freedom).</p>a<p>Risk group determined according to model published in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001664#pmed.1001664-Perel1" target="_blank">[10]</a>.</p

Mortality by category of predicted risk of death and red blood cell transfusion excluding deaths on day 0.

<p>Interaction between RBC transfusion and predicted risk of death on the OR, <i>p<</i>0.0001 (chi-square <i> = </i>150 with one degree of freedom).</p>a<p>Risk group determined according to model published in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001664#pmed.1001664-Perel1" target="_blank">[10]</a>.</p

Mortality by category of predicted risk of death and red blood cell transfusion adjusted for propensity score.

<p>Interaction between RBC transfusion and predicted risk of death on the OR, <i>p<</i>0.0001 (chi-square <i> = </i>151).</p>a<p>Risk group determined according to model published in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001664#pmed.1001664-Perel1" target="_blank">[10]</a>.</p

Baseline characteristics by transfusion status.

<p>Data are presented as number, number (percent), or median (interquartile range).</p>a<p>From a logistic regression model fitting each covariate as a categorical or continuous variable. Predicted risk of death was not calculated for those with missing values.</p

Vascular occlusive events (fatal and non-fatal) by category of predicted risk of death and red blood cell transfusion.

<p>Interaction between RBC transfusion and predicted risk of death on the OR, <i>p = </i>0.013.</p>a<p>Risk group determined according to model published in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001664#pmed.1001664-Perel1" target="_blank">[10]</a>.</p