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1.
Microbiol Spectr ; 10(3): e0005022, 2022 06 29.
Article in English | MEDLINE | ID: mdl-35678554

ABSTRACT

The nasopharyngeal commensal Streptococcus pneumoniae can become invasive and cause metastatic infection. This requires the pneumococcus to have the ability to adapt, grow, and reside in diverse host environments. Therefore, we studied whether the likelihood of severe disease manifestations was related to pneumococcal growth kinetics. For 383 S. pneumoniae blood isolates and 25 experimental mutants, we observed highly reproducible growth curves in nutrient-rich medium. The derived growth features were lag time, maximum growth rate, maximum density, and stationary-phase time before lysis. First, the pathogenicity of each growth feature was probed by comparing isolates from patients with and without marked preexisting comorbidity. Then, growth features were related to the propensity of causing severe manifestations of invasive pneumococcal disease (IPD). A high maximum bacterial density was the most pronounced pathogenic growth feature, which was also an independent predictor of 30-day mortality (P = 0.03). Serotypes with an epidemiologically higher propensity for causing meningitis displayed a relatively high maximum density (P < 0.005) and a short stationary phase (P < 0.005). Correspondingly, isolates from patients diagnosed with meningitis showed an especially high maximum density and short stationary phase compared to isolates from the same serotype that had caused uncomplicated bacteremic pneumonia. In contrast, empyema-associated strains were characterized by a relatively long lag phase (P < 0.0005), and slower growth (P < 0.005). The course and dissemination of IPD may partly be attributable to the pneumococcal growth features involved. If confirmed, we should tailor the prevention and treatment strategies for the different infection sites that can complicate IPD. IMPORTANCE Streptococcus pneumoniae is a leading infectious cause of deaths worldwide. To understand the course and outcome of pneumococcal infection, most research has focused on the host and its response to contain bacterial growth. However, bacterial epidemiology suggest that certain pneumococcal serotypes are particularly prone to causing complicated infections. Therefore, we took the bacterial point of view, simply examining in vitro growth features for hundreds of pneumococcal blood isolates. Their growth curves were very reproducible. Certain poles of pneumococcal growth features were indeed associated with specific clinical manifestations like meningitis or pleural empyema. This indicates that bacterial growth style potentially affects the progression of infection. Further research on bacterial growth and adaptation to different host environments may therefore provide key insight into pathogenesis of complicated invasive disease. Such knowledge could lead to more tailored vaccine targets or therapeutic approaches to reduce the million deaths that are caused by pneumococcal disease every year.


Subject(s)
Meningitis , Pneumococcal Infections , Humans , Infant , Pneumococcal Infections/microbiology , Pneumococcal Vaccines , Serogroup , Serotyping , Streptococcus pneumoniae
2.
Sci Rep ; 5: 12758, 2015 Aug 03.
Article in English | MEDLINE | ID: mdl-26234525

ABSTRACT

Innate immunity is the first line of defence against pathogens and is essential for survival of the infected host. The fruit fly Drosophila melanogaster is an emerging model to study viral pathogenesis, yet antiviral defence responses remain poorly understood. Here, we describe the heat shock response, a cellular mechanism that prevents proteotoxicity, as a component of the antiviral immune response in Drosophila. Transcriptome analyses of Drosophila S2 cells and adult flies revealed strong induction of the heat shock response upon RNA virus infection. Dynamic induction patterns of heat shock pathway components were characterized in vitro and in vivo following infection with different classes of viruses. The heat shock transcription factor (Hsf), as well as active viral replication, were necessary for the induction of the response. Hsf-deficient adult flies were hypersensitive to virus infection, indicating a role of the heat shock response in antiviral defence. In accordance, transgenic activation of the heat shock response prolonged survival time after infection and enabled long-term control of virus replication to undetectable levels. Together, our results establish the heat shock response as an important constituent of innate antiviral immunity in Drosophila.


Subject(s)
Drosophila/virology , Heat-Shock Response/physiology , Host-Pathogen Interactions , Animals , Animals, Genetically Modified , Cells, Cultured , DNA Viruses/pathogenicity , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drosophila/immunology , Drosophila/physiology , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Female , Gene Expression Profiling , Gene Expression Regulation , Heat Shock Transcription Factors , Male , RNA Interference , Transcription Factors/genetics , Transcription Factors/metabolism , Viral Load , Virus Diseases/etiology , Virus Diseases/veterinary
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