The globally prominent pathogen secretes potent immunomodulatory proteins known as superantigens (SAgs), which engage lateral surfaces of major histocompatibility class II molecules and T-cell receptor (TCR) β-chain variable domains (Vβs). These interactions result in the activation of numerous Vβ-specific T cells, which is the defining activity of a SAg. Although streptococcal SAgs are known virulence factors in scarlet fever and toxic shock syndrome, mechanisms by how SAgs contribute to the life cycle of remain poorly understood. Herein, we demonstrate that passive immunization against the Vβ8-targeting SAg streptococcal pyrogenic exotoxin A (SpeA), or active immunization with either wild-type or a nonfunctional SpeA mutant, protects mice from nasopharyngeal infection; however, only passive immunization, or vaccination with inactive SpeA, resulted in high-titer SpeA-specific antibodies in vivo. Mice vaccinated with wild-type SpeA rendered Vβ8 T cells poorly responsive, which prevented infection. This phenotype was reproduced with staphylococcal enterotoxin B, a heterologous SAg that also targets Vβ8 T cells, and rendered mice resistant to infection. Furthermore, antibody-mediated depletion of T cells prevented nasopharyngeal infection by , but not by, a bacterium that does not produce SAgs. Remarkably, these observations suggest that uses SAgs to manipulate Vβ-specific T cells to establish nasopharyngeal infection.

Meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection is responsible for significant morbidity, with mortality rates as high as 60 % if not treated appropriately. We describe a rapid method to detect MRSA in blood cultures using a combined three-hour shortincubation BRUKER matrix-assisted laser desorption/ionization time-of-flight MS BioTyper protocol and a qualitative immunochromatographic assay, the Alere Culture Colony Test PBP2a detection test. We compared this combined method with a molecular method detecting the nuc and mecA genes currently performed in our laboratory. One hundred and seventeen S. aureus blood cultures were tested of which 35 were MRSA and 82 were meticillin-sensitive S. aureus (MSSA). The rapid combined test correctly identified 100 % (82/82) of the MSSA and 85.7 % (30/35) of the MRSA after 3 h. There were five false negative results where the isolates were correctly identified as S. aureus, but PBP2a was not detected by the Culture Colony Test. The combined method has a sensitivity of 87.5 %, specificity of 100 %, a positive predictive value of 100 % and a negative predictive value of 94.3 % with the prevalence of MRSA in our S. aureus blood cultures. The combined rapid method offers a significant benefit to early detection of MRSA in positive blood cultures. INTRODUCTIONStaphylococcus aureus is a clinically important pathogen that causes a wide variety of diseases and accounts for more than 50 % of nosocomial infections in intensive care units (NNIS System, 1999). S. aureus bacteraemia (SAB) is an infection of the blood associated with a mortality rate in excess of 20 % (Klevens et al., 2006;Lowy, 1998) while meticillin-resistant S. aureus (MRSA) bacteraemia is associated with mortality rates as high as 60 % (Cluff et al., 1968;Julander, 1985).Until the 1980s, MRSA was almost exclusively limited to nosocomial settings and community strains were largely considered meticillin susceptible (Thompson et al., 1982). However, a decade later there was a measurable increase in community-acquired meticillin-resistant S. aureus (CA-MRSA) infections in people with no known risk factors and an overall increase in CA-MRSA infections in general (Layton et al., 1995). In Canada, there was a 17-fold increase in CA-MRSA infections from 1995 to (Simor et al., 2010. In London, Ontario, the all-cause mortality Abbreviations: BAP, blood agar plate; CA-MRSA, community-acquired meticillin-resistant Staphylococcus aureus; CCT, Alere PBP2a Culture Colony Test; CI, confidence interval; MALDI-ToF, matrix-assisted laser desorption/ionization time-of-flight; MRSA, meticillin-resistant S. aureus; MSSA, meticillin-sensitive S. aureus; OR, odds ratio; SAB, S. aureus bacteraemia; SIMI, short-incubation MALDI-ToF MS identification. Cavassini et al., 1999). Some of these methods depend on well-defined colony morphology and can be very time and labour intensive. To the best of our knowledge, a combined rapid, 3 h procedure, using a shortincubationThe objective of this study was to determine the ability t...