Toxic shock syndrome (TSS) is an acute onset illness characterized by fever, rash formation, and hypotension that can lead to multiple organ failure and lethal shock, as well as desquamation in patients that recover. The disease is caused by bacterial superantigens (SAGs) secreted from Staphylococcus aureus and group A streptococci. SAGs bypass normal antigen presentation by binding to class II major histocompatibility complex molecules on antigen-presenting cells and to specific variable regions on the beta-chain of the T-cell antigen receptor. Through this interaction, SAGs activate T cells at orders of magnitude above antigen-specific activation, resulting in massive cytokine release that is believed to be responsible for the most severe features of TSS. This review focuses on clinical and epidemiological aspects of TSS, as well as important developments in the genetics, biochemistry, immunology, and structural biology of SAGs. From the evolutionary relationships between these important toxins, we propose that there are five distinct groups of SAGs.

Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. There is now mounting evidence that selected probiotic strains can provide health benefits to their human hosts. Numerous clinical trials show that certain strains can improve the outcome of intestinal infections by reducing the duration of diarrhea. Further investigations have shown benefits in reducing the recurrence of urogenital infections in women, while promising studies in cancer and allergies require research into the mechanisms of activity for particular strains and better-designed trials. At present, only a small percentage of physicians either know of probiotics or understand their potential applicability to patient care. Thus, probiotics are not yet part of the clinical arsenal for prevention and treatment of disease or maintenance of health. The establishment of accepted standards and guidelines, proposed by the Food and Agriculture Organization of the United Nations and the World Health Organization, represents a key step in ensuring that reliable products with suitable, informative health claims become available. Based upon the evidence to date, future advances with single- and multiple-strain therapies are on the horizon for the management of a number of debilitating and even fatal conditions

Genome sequences are available for many bacterial strains, but there has been little progress in using these data to understand the molecular basis of pathogen emergence and differences in strain virulence. Serotype M3 strains of group A Streptococcus (GAS) are a common cause of severe invasive infections with unusually high rates of morbidity and mortality. To gain insight into the molecular basis of this high-virulence phenotype, we sequenced the genome of strain MGAS315, an organism isolated from a patient with streptococcal toxic shock syndrome. The genome is composed of 1,900,521 bp, and it shares Ϸ1.7 Mb of related genetic material with genomes of serotype M1 and M18 strains. Phage-like elements account for the great majority of variation in gene content relative to the sequenced M1 and M18 strains. Recombination produces chimeric phages and strains with previously uncharacterized arrays of virulence factor genes. Strain MGAS315 has phage genes that encode proteins likely to contribute to pathogenesis, such as streptococcal pyrogenic exotoxin A (SpeA) and SpeK, streptococcal superantigen (SSA), and a previously uncharacterized phospholipase A2 (designated Sla). Infected humans had anti-SpeK, -SSA, and -Sla antibodies, indicating that these GAS proteins are made in vivo. SpeK and SSA were pyrogenic and toxic for rabbits. Serotype M3 strains with the phage-encoded speK and sla genes increased dramatically in frequency late in the 20th century, commensurate with the rise in invasive disease caused by M3 organisms. Taken together, the results show that phagemediated recombination has played a critical role in the emergence of a new, unusually virulent clone of serotype M3 GAS.superantigen ͉ streptococcal pyrogenic exotoxin ͉ comparative genomics

BackgroundThe lack of a reliable scoring system that predicts the development of septic shock and death precludes comparison of disease and/or treatment outcomes in animal models of sepsis. We developed a murine sepsis score (MSS) that evaluates seven clinical variables, and sought to assess its validity and reliability in an experimental mouse model of polymicrobial sepsis.MethodsStool collected from the cecum of C57BL/6 (B6) mice was dissolved in 0.9% normal saline (NS) and filtered, resulting in a fecal solution (FS) which was injected intraperitoneally into B6 mice. Disease severity was monitored by MSS during the experimental timeline. Blood and tissue samples were harvested for the evaluation of inflammatory changes after sepsis induction. The correlation between pro-inflammatory markers and MSS was assessed by the Spearman rank correlation coefficient.ResultsMice injected with FS at a concentration of 90 mg/mL developed polymicrobial sepsis with a 75% mortality rate at 24 hours. The MSS was highly predictive of sepsis progression and mortality, with excellent discriminatory power, high internal consistency (Cronbach alpha coefficient = 0.92), and excellent inter-rater reliability (intra-class coefficient = 0.96). An MSS of 3 had a specificity of 100% for predicting onset of septic shock and death within 24 hours. Hepatic dysfunction and systemic pro-inflammatory responses were confirmed by biochemical and cytokine analyses where the latter correlated well with the MSS. Significant bacterial dissemination was noted in multiple organs. Furthermore, the liver, spleen, and intestine demonstrated histopathological evidence of injury.ConclusionsThe MSS reliably predicts disease progression and mortality in an animal model of polymicrobial sepsis. More importantly, it may be used to assess and compare outcomes among various experimental models of sepsis, and serve as an ethically acceptable alternative to death as an endpoint.