Microorganisms live in most parts of our body, including the inside of our nose. Most of the microbes are harmless and can even be beneficial to our health. However, some microbes can cause diseases – although they often go unnoticed, as our immune system can remove them before we show any symptoms.
Completed project
For example, the bacterium Streptococcus pneumoniae can cause diseases such as pneumonia and meningitis, but generally, it lives harmlessly in the nose, and is particularly common in children and the elderly. The longer the bacteria live in the nose before being killed by the immune system, the more likely they are to be transmitted to another person. The amount of time it takes for the immune system to clear the bacteria depends on various factors, such as the age of the person or the bacterium’s defense mechanism and its genetic material. A particularly important aspect is to what subtype, also known as serotype, a bacterium belongs to, which is characterized by differences in the structure of the sugar coating that surrounds the microbe. However, until now, it was not known how much each of these factors contributes.
This project provides new information for understanding the processes of evolution within the host and the mechanisms by which antibiotic treatment can influence the selection for antibiotic resistance.
Project partners
- Stephen Bentley, The Wellcome Trust Sanger Institute, United Kingdom (Coordinator)
- Nahuel Fittipaldi, Public Health Ontario Laboratories, Canada
- James Kellner, University of Calgary, Canada
- Bernd Schmeck, Philipps-University Marburg, Germany
- Paul Turner, University of Oxford, United Kingdom
- Tom van der Poll, Academic Medical Center University of Amsterdam, Netherlands
- Nicolas Croucher, Imperial College London, United Kingdom
Project resources
Video
The Global Pneumococcal Sequencing (GPS) project: How can whole-genome sequencing be used to make vaccines more effective?
Publications
- Front Pediatr, 2021. Carriage Dynamics of Pneumococcal Serotypes in Naturally Colonized Infants in a Rural African Setting During the First Year of Life
- Communications Biology volume, 2020. Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism
- Nature Communications, 2020. Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation.
- Scand J Immunol, 2020. Metabolic adaptations of human alveolar macrophages upon activation by lipopolysaccharide in vivo
- Frontiers in Immunology, 2019. Peptidoglycan Recognition Protein 4 Limits Bacterial Clearance and Inflammation in Lungs by Control of the Gut Microbiota
- International Journal of Chronic Obstructive Pulmonary Disease, 2019. Personalized medicine for patients with COPD: where are we?
- Scientific Reports, 2021. Novel computational analysis of large transcriptome datasets identifies sets of genes distinguishing chronic obstructive pulmonary disease from healthy lung samples.
- Advanced Drug Delivery Reviews, 2021. The clinical role of host and bacterial-derived extracellular vesicles in pneumonia
- Mediators of Inflammation, 2021. Hypoxia-Inducible Factor-1α in Macrophages, but Not in Neutrophils, Is Important for Host Defense during Klebsiella pneumoniae-Induced Pneumosepsis
- FASEB J. 2020. Influenza virus-mediated suppression of bronchial Chitinase-3-like 1 secretion promotes secondary pneumococcal infection.
- PLoS Comput Biol. 2020. Detection and segmentation of morphologically complex eukaryotic cells in fluorescence microscopy images via feature pyramid fusion.
- J Cyst Fibros. 2021. Defective BACH1/HO-1 regulatory circuits in cystic fibrosis bronchial epithelial cells.
- Proc Natl Acad Sci U S A. 2020. Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway.
- mBio. 2020. A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1.
- Sci Rep. 2020. Transcriptional analysis identifies potential biomarkers and molecular regulators in pneumonia and COPD exacerbation
- Cell Signal. 2020. NF-κB-mediated inhibition of microRNA-149-5p regulates Chitinase-3-like 1 expression in human airway epithelial cells.
- Nat Commun. 2019. IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
- Virulence. 2019. Antibacterial activity of a Tribolium castaneum defensin in an in vitro infection model of Streptococcus pneumoniae.
- J Infect Dis. 2020. Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
- J Virol. 2019. TMPRSS2 Is the Major Activating Protease of Influenza A Virus in Primary Human Airway Cells and Influenza B Virus in Human Type II Pneumocytes.
- J Clin Invest. 2019. Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells.
- Nat Microbiol. 2019. Intracellular bacteria engage a STING-TBK1-MVB12b pathway to enable paracrine cGAS-STING signalling.
- Methods Mol Biol. 2019. ncRNAs in Inflammatory and Infectious Diseases.
- Mol Biol Evol. 2021. Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models.
- Sci Rep. 2020. Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity.
- Annals of Intensive Care, 2021. Association between delay in intensive care unit admission and the host response in patients with community-acquired pneumonia
