_JPIAMR_pneumo_transmission. _JPIAMR_pneumo_transmission

Streptococcus pneumoniae is a major health threat in industrialized and developing countries, young and old people, immune-competent as well as immunocompromised hosts. By genetic recombination within diverse populations, individual strains are not only able to evade vaccination but also able to acquire antibiotic resistance, which can then be transmitted onwards. This proposal aims to understand the mechanisms and distribution of this pneumococcal resistance repertoire at genetic, bacterial, host and population levels to layout new strategies for risk assessment, prevention and reduction of antimicrobial resistance. 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. Therefore, a multinational consortium of complementary expertise has been formed: Clinically important and newly emerged resistant pneumococcal strains of together with the related patient characteristics (clinical, genetic, and transcriptomic data) are available from Canadian and German cohorts as well as highly detailed carriage sampling from a Thai cohort. This is complemented with expertise in bacterial genetics, microbiology, bioinformatics, in vivo/in vitro models as well as by paediatric and adult clinical researchers. Taken together, 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. The Sanger role in this project is to study the relationship between pneumococcal transmission, antibiotic resistance and antibiotic consumption by analysing pneumococcal genome data generated from samples collected from donors and recipients in transmission events identified in the Maela carriage study. We aim to carefully quantify the effect page 1 [A3] Please provide text (abstract) which will accompany data for this study in the ENA/EGA. [A4] Does this project use samples? [A8] Please state the anticipated project start date (month/year). [A9] Please state the project duration (months). [A10] Please read WTSI's Data Sharing Policy and Guidelines, then explain your data sharing plans for the project [A11] Are the data sharing plans of this project compliant with the Institute's Guidelines? [A15] Are there any conflicts of interest related to this proposal? that antibiotic consumption has on the dynamics of carriage and transmission in the pneumococcus, information which will be valuable in understanding how antibiotic resistance increases in prevavlance and may inform strategies to reduce the effect. To provide sufficient data to identify and confirm transmission events and to detect relatively small effects of antibiotic consumption we estimate a need to sequence 5000 genomes - this project fits well with the QQ plan and we anticipate this sequencing to be funded internally (internal prelim submitted I2500). This prelim is for 3rd party funding from MRC under the JPI-EC-AMR call and for Sanger is largely to fund a 3 year postdoc position for genome data analysis and mathematical modelling. 1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/