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

Streptococcus pneumoniae is a major health threat in industrialised 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.

Aim

This project aimed 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.

Methods

The project was carried out by an international consortium with diverse areas of expertise, using existing patient cohorts, collections of pneumococcal strains, and mouse models of infection.

Results

Amsterdam UMC studied host-pathogen interaction in pneumococcal infections in several ways. In culture systems, the mechanisms contributing to the activation of airway epithelium and macrophages by pneumococci were identified. In mouse models of upper respiratory tract colonisation and lower respiratory tract infection by pneumococci, the role of immune cells and the energy supply of immune cells in the immune response was investigated. Analysis of patients with documented pneumococcal pneumonia or pneumonia caused by other pathogens showed similarities but also some differences between the host response elicited by different microorganisms.