Browsing by Subject "PYOGENES"

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  • Pesola, A. K.; Sihvonen, R.; Lindholm, L.; Patari-Sampo, A. (2015)
    In 2012, blood, skin and soft tissue infections caused by clindamycin resistant Streptococcus pyogenes (group A streptococcus; GAS) appeared to be increasing in the Helsinki metropolitan area. We compared monthly percentages of clindamycin resistant isolates in the area between 2012 and 2013, with those in 2010 and 2011. Resistance frequency in terms of patient age was also studied. We reviewed the medical records of bacteraemic cases in 2012 and 2013 and linked the data to emm types. To inform on the emm distribution among GAS isolated from skin and soft tissue infections during the epidemic, GAS isolates of one month (March 2013) were emm typed. For GAS blood, skin, and soft tissue isolates taken together, the proportions of clindamycin resistant isolates were significantly higher in 2012 and 2013 (23% and 17%, respectively) compared with the two previous years (3%, p
  • Kachroo, Priyanka; Eraso, Jesus M.; Olsen, Randall J.; Zhu, Luchang; Kubiak, Samantha L.; Pruitt, Layne; Yerramilli, Prasanti; Cantu, Concepcion C.; Saavedra, Matthew Ojeda; Pensar, Johan; Corander, Jukka; Jenkins, Leslie; Kao, Lillian; Granillo, Alejandro; Porter, Adeline R.; DeLeo, Frank R.; Musser, James M. (2020)
    A fundamental goal of contemporary biomedical research is to understand the molecular basis of disease pathogenesis and exploit this information to develop targeted and more-effective therapies. Necrotizing myositis caused by the bacterial pathogen Streptococcus pyogenes is a devastating human infection with a high mortality rate and few successful therapeutic options. We used dual transcrip-tome sequencing (RNA-seq) to analyze the transcriptomes of S. pyogenes and host skeletal muscle recovered contemporaneously from infected nonhuman primates. The in vivo bacterial transcriptome was strikingly remodeled compared to organisms grown in vitro, with significant upregulation of genes contributing to virulence and altered regulation of metabolic genes. The transcriptome of muscle tissue from infected nonhuman primates (NHPs) differed significantly from that of mock-infected animals, due in part to substantial changes in genes contributing to inflammation and host defense processes. We discovered significant positive correlations between group A streptococcus (GAS) virulence factor transcripts and genes involved in the host immune response and inflammation. We also discovered significant correlations between the magnitude of bacterial virulence gene expression in vivo and pathogen fitness, as assessed by previously conducted genome-wide transposon-directed insertion site sequencing (TraDIS). By integrating the bacterial RNA-seq data with the fitness data generated by TraDIS, we discovered five new pathogen genes, namely, S. pyogenes 0281 (Spy0281 [dahA]), ihk-irr, slr, isp, and ciaH, that contribute to necrotizing myositis and confirmed these findings using isogenic deletion-mutant strains. Taken together, our study results provide rich new information about the molecular events occurring in severe invasive infection of primate skeletal muscle that has extensive translational research implications. IMPORTANCE Necrotizing myositis caused by Streptococcus pyogenes has high morbidity and mortality rates and relatively few successful therapeutic options. In addition, there is no licensed human S. pyogenes vaccine. To gain enhanced understanding of the molecular basis of this infection, we employed a multidimensional analysis strategy that included dual RNA-seq and other data derived from experimental infection of nonhuman primates. The data were used to target five streptococcal genes for pathogenesis research, resulting in the unambiguous demonstration that these genes contribute to pathogen-host molecular interactions in necrotizing infections. We exploited fitness data derived from a recently conducted genome-wide transposon mutagenesis study to discover significant correlation between the magnitude of bacterial virulence gene expression in vivo and pathogen fitness. Collectively, our findings have significant implications for translational research, potentially including vaccine efforts.
  • Laakso, Juha T.; Rissanen, Valtteri; Ruotsalainen, Eeva; Korpi, Jarkko; Laulajainen-Hongisto, Anu; Sivonen, Ville; Sinkkonen, Saku T. (2021)
    Objective To describe the characteristics, diagnostics, treatment, and outcome of severe acute otitis media (AOM) and acute mastoiditis (AM) caused by group A beta-hemolytic streptococcus (GAS). Study design A retrospective cohort study. Methods The yearly incidence of inpatient care-needing GAS AOM/AM patients in our hospital catchment area between 2002 and 2018 was investigated. A detailed analysis was performed for cases treated during the last GAS epidemic in 2017-2018. Anamnesis, signs and symptoms, pure-tone audiometry results, treatment, complications, and outcome were collected from medical charts. Patients responded to an otology-specific health-related quality of life survey (EOS-16) 1.5 to 3 years after their treatment. Results The number of GAS infections peaks at approximately 7-year intervals. During 2017 and 2018, altogether 37 patients (29 adults and 8 children) were hospitalized due to GAS AOM/AM. AM was diagnosed in 14 (38%) patients. The disease progression was typically very rapid. At presentation, all patients had severe ear pain, 68% tympanic membrane perforation and discharge, 43% fever, and 43% vertigo. In pure-tone audiometry, there was usually a marked mixed hearing loss at presentation. There was a significant recovery in both air and bone conduction thresholds; the pure tone average improvement from presentation was 32.3 +/- 14.8 dB. Rapid strep tests (RST) proved to be more sensitive than bacterial culture in identifying GAS as a cause of AOM/AM. Conclusion GAS AOM/AM has a rapid onset. Hearing loss usually includes a sensorineural component, which is usually reversible with adequate treatment. RST seems to be useful in detecting GAS from middle ear discharge. Level of Evidence 4.