Long_term_population_dynamics_of_Escherichia_coli_causing_bloodstream_infection_in_Malawi

Escherichia coli is one of the leading causes of bloodstream infection (BSI) across the globe, and specifically in sub-Saharan Africa. In Malawi, therapeutic options for E. coli BSI are being seriously limited by the emergence ESBL-producing E. coli (ESBL-Ec), which have expanded rapidly since the introduction of third generation cephalosporins into routine use in 2005. Despite the changing antimicrobial susceptibility patterns, the diversity and population structure of BSI causing E. coli and how it is changing over time, remains elusive. We will undertake a whole genome sequencing study to investigate the population dynamics of E. coli causing BSI in Malawi using a longitudinal collection of blood culture E. coli isolates collected over a period that spans over twenty years from patients presenting with bloodstream infection to Queen Elizabeth Central Hospital in Malawi. These isolates have been archived at the Malawi-Liverpool-Wellcome Programme, in Blantyre, Malawi. We will use phylogenetic analysis and genomic clustering approaches to describe the population structure and dynamics of BSI E. coli. We will also screen for and characterise AMR genes and virulence factors over time to understand their emergence in different E. coli lineages. We will put these datasets in context of a large collection of carriage ESBL-Ec genomes from the same setting, which we have sequenced under the DRUM (Drivers of antimicrobial resistance in Uganda and Malawi) study, to understand the role of ESBL carriage lineages in bloodstream infection.