Predicting the virulence of MRSA from its genome sequence. aureus? A comparative cohort study of British patients with nosocomial infection and bacteraemia. Is methicillin- resistant Staphylococcus aureus more virulent than methicillin-susceptible S. Risk of death from methicillin-resistant Staphylococcus aureus bacteraemia: a meta-analysis. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteraemia: a meta-analysis. Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteraemia and abscess formation. Cytotoxic virulence predicts mortality in nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus. Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus. Characterization of alpha-toxin hla gene variants, alpha-toxin expression levels, and levels of antibody to alpha-toxin in hemodialysis and postsurgical patients with Staphylococcus aureus bacteraemia. α-Hemolysin, not Panton–Valentine leukocidin, impacts rabbit mortality from severe sepsis with methicillin-resistant Staphylococcus aureus osteomyelitis. Differential expression and roles of Staphylococcus aureus virulence determinants during colonization and disease. Predictors of mortality in Staphylococcus aureus bacteraemia. Incidence of invasive methicillin-resistant Staphylococcus aureus infections in Germany, 2010 to 2014. Population dynamics of Staphylococcus aureus from northeastern Nigeria in 20. difficile Infection Data 2015/16 (Public Health England, 2016) 46, S350–S359 (2008).Īnnual Epidemiological Commentary: Mandatory MRSA, MSSA and E. Pathogenesis of methicillin-resistant Staphylococcus aureus infection. This strongly suggests that existing infection control and treatment options are insufficient to tackle this important health problem and that a better understanding of the factors that contribute to bacteraemia-associated morbidity is crucially needed. Furthermore, the 30-day (all-cause) mortality rate for SAB has not significantly changed over the last two decades and appears to have plateaued at approximately 20% (ref. However, in the UK, the incidence of methicillin-susceptible SAB has been increasing year on year, with an overall increase of more than 15% since reporting became mandatory in 2011/2012 (ref. Mandatory surveillance of SAB has been implemented in several countries, with many reporting a decline in the incidence of methicillin-resistant SAB 3, 4, 5. The bacterium Staphylococcus aureus bacteraemia (SAB) is a significant global health problem 1 and is exacerbated by the emergence and widespread circulation of drug-resistant strains such as methicillin-resistant S. Our study further demonstrates the use of a combined genomics and data analytic approach to enhance our understanding of bacterial pathogenesis at the individual level, which will be an important step towards personalized medicine and infectious disease management. Our results therefore suggest that different clones may have adopted different strategies to overcome host responses and cause severe pathology. Whereas elevated cytolytic toxicity in combination with low levels of biofilm formation was predictive of an increased risk of mortality in infections by strains of a CC22 background, these virulence-specific factors had little influence on mortality rates associated with CC30 infections. By analysing the pooled data comprising bacterial genotype and phenotype together with clinical metadata within a machine-learning framework, we found significant clonal differences in the determinants most predictive of poor infection outcome. By adopting a genome-wide association study approach we identified and functionally verified several genetic loci that affect the expression of cytolytic toxicity and biofilm formation. aureus isolates from patients with bloodstream infections, representing two globally important clonal types, CC22 and CC30. To investigate the role of bacterial factors in contributing to bacteraemia-associated mortality, we phenotyped a collection of sequenced clinical S. The role of the bacterium in infection severity is less well understood, as it is complicated by the multifaceted nature of bacterial virulence, which has so far prevented a robust mapping between genotype, phenotype and infection outcome. Infection severity, and in particular bacteraemia-associated mortality, has been attributed to several host-related factors, such as age and the presence of comorbidities. The bacterium Staphylococcus aureus is a major human pathogen for which the emergence of antibiotic resistance is a global public health concern.
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