Project description:D’Mello et al. detail host-pathogen interaction gene expression profiles of Streptococcus pneumoniae (Spn) and its infected host at disease relevant anatomical sites using mice as experimental models. The authors identify the core and organ-specific transcriptomes of Spn, show that bacterial and host gene expression profiles are highly distinct during asymptomatic colonization versus disease-causing infection, and demonstrate that Spn and host genes with high levels of expression contribute to pathogenesis or host defense, respectively.
Project description:The transcriptomic innate immune response derived from human nasal epithelial cells depends on how Streptococcus pneumoniae colonises the nasopharynx. This study compared three wild type strains and one deficient in pneumolysin to explore the pathways of epithelial activation following a three hour infection in vitro.
Project description:Transcriptional effects in liver, lung and blood samples from mice after intratracheal challenge with either Streptococcus pneumoniae serotype 19 (lobar-pneumonia) or serotype 2 (sepsis) were monitored after 6 and 24 hours and compared to sham (vehicle control). We gratefully acknowledge the BMBF grant within the “Promoting global research excellence in severe sepsis” (PROGRESS) study (01KI07111).
Project description:Vaccine-enhanced disease (VED) occurs as a result of vaccination followed by infection with virulent Mycoplasma pneumoniae. To date, VED has prevented development of an efficacious vaccine against this significant human respiratory pathogen. Herein we report that vaccination with M. pneumoniae lipid-associated membrane proteins (LAMPs) induces lung lesions consistent with exacerbated disease following challenge, without reducing bacterial loads. Removal of lipid moieties from LAMPs prior to vaccination eliminates VED and reduces bacterial loads after infection. Collectively, these data indicate that lipid moieties of lipoproteins are the causative factors of M. pneumoniae VED.
Project description:Streptococcus pneumoniae colonization in the upper respiratory tract is linked to pneumococcal disease development, predominantly affecting young children and older adults. As the global population ages and comorbidities increase, there is a heightened concern about this infection. We investigated the immunological responses of older adults to pneumococcal controlled human infection by analysing the cellular composition and gene expression in the nasal mucosa. Our comparative analysis with data from a concurrent study in younger adults revealed distinct gene expression patterns in older individuals susceptible to colonization, highlighted by neutrophil activation and elevated levels of CXCL9 and CXCL10. Unlike younger adults challenged with pneumococcus, older adults did not show recruitment of monocytes into the nasal mucosa following nasal colonization. However, older adults who were protected from colonization showed increased degranulation of CD8+ T cells, both before and after pneumococcal challenge. These findings suggest age-associated cellular changes, in particular enhanced mucosal inflammation, that may predispose older adults to pneumococcal colonization.
Project description:Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown.
This study includes 1146 samples of host genotyping data (genotyped and imputed) from Illumina Omni arrays. Samples were collected from adults (>16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015. Metadata includes patient outcome, species of bacteria, and for 467 samples a link to an ENA run with the associated bacterial genome (S. pneumoniae only).
Project description:Transcriptional effects in liver, lung and blood samples from mice after intratracheal challenge with either Streptococcus pneumoniae serotype 19 (lobar-pneumonia) or serotype 2 (sepsis) were monitored after 6 and 24 hours and compared to sham (vehicle control). We gratefully acknowledge the BMBF grant within the “Promoting global research excellence in severe sepsis” (PROGRESS) study (01KI07111). Three tissues x two serotypes x two time resolved treatment groups x four replicates, three tissues x Sham Control x three replicates.
Project description:Rapid adaptation to grow within the physiological conditions found in the host environment is an essential but poorly understood virulence requirement for systemic pathogens such as Streptococcus pneumoniae. We have now demonstrated an essential role for the one-carbon metabolism pathway and a conditional role depending on strain background for proline biosynthesis for S. pneumoniae growth in serum or CSF and therefore for systemic virulence. RNAseq data demonstrated that loss of one carbon metabolism or proline biosynthesis both have profound but differing effects on S. pneumoniae metabolism in human serum, identifying the metabolic processes dependent on each pathway during systemic infection. These data provide a more detailed understanding of the adaptations required by systemic bacterial pathogens in order to cause infection, and demonstrate that the requirement for some of these adaptations vary between strains from the same species and could therefore underpin strain variations in virulence potential.
Project description:Epithelial cells are the first point of contact for bacteria entering the respiratory tract. Streptococcus pneumoniae is an obligatory human pathobiont of the nasal mucosa, carried asymptomatically but also the cause of severe pneumoniae. The role of the epithelium in maintaining homeostatic interactions or mounting an inflammatory response to invasive S. pneumoniae is currently poorly understood. However, studies have shown that chromatin modifications, at the histone level, induced by bacterial pathogens interfere with the host transcriptional program and promote infection. In this study, we demonstrate that S. pneumoniae actively induces di-methylation of histone H3 on lysine 4 (H3K4me2), which persists for at least 9 days upon clearance of bacteria with antibiotics. We show that infection establishes a unique epigenetic program affecting the transcriptional response of epithelial cells, rendering them more permissive upon secondary infection. Our results establish H3K4me2 as a unique modification induced by infection, distinct from H3K4me3, which localizes to enhancer regions genome-wide. Therefore, this study reveals evidence that bacterial infection leaves a memory in epithelial cells after bacterial clearance, in an epigenomic mark, thereby altering cellular responses for subsequent infections.
