Prevention and Restriction of Antimicrobial Resistance in Pneumococci by Multi-Level Modelling



Research Project: 2017-07-03 - 2021-09-10
Total sum awarded: €1 704 563

Streptococcus pneumoniae is a major health threat in industrialized and developing countries. The pathogen affects both young and old people, immune-competent as well as immunocompromised individuals. By genetic recombination within diverse populations, individual strains are not only able to evade vaccination but also able to acquire antimicrobial resistance (AMR), which can then be transmitted onwards. This proposal aims to understand the mechanisms and distribution of this pneumococcal AMR repertoire at the genetic, bacterial, host and population levels to layout new strategies for risk assessment, prevention and reduction of AMR. In particular, the environmental, immunological and pharmacological drivers of resistance emergence and selection, the genetic population dynamics, as well as the fitness of the new traits in different host conditions will be analysed and modelled. To this end, a multinational consortium of researchers with complementary expertise has been formed. Available to the consortium are clinically important and newly emerged pneumococcal AMR strains, together with related patient metadata (clinical, genetic and transcriptomic) from clinical cohorts as well as highly detailed carriage sampling from a Thai cohort. Consortium members have proven expertise in microbiology, bacterial genetics, bioinformatics, in vivo/in vitro models while others are clinicians expert in the treatment of pneumococcal infections in both paediatric and adult patients. In a concerted effort, this consortium will develop countermeasures against antimicrobial resistance in a major health threat by multi-level modelling of its resistance emergence, selection, and transmission in diverse environments.

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  • Stephen Bentley, The Wellcome Trust Sanger Institute, United Kingdom (Coordinator)
  • Nahuel Fittipaldi, Public Health Ontario Laboratories, Canada (Partner)
  • James Kellner, University of Calgary, Canada (Partner)
  • Bernd Schmeck, Philipps-University Marburg, Germany (Partner)
  • Paul Turner, University of Oxford, United Kingdom (Partner)
  • Tom van der Poll, University of Amsterdam, Netherlands (Partner)
  • Nicolas Croucher, Imperial College London, United Kingdom (Observer)

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. 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.