Drivers_of_antimicrobial_resistance_in_Uganda_and_Malawi

The Drivers of antimicrobial resistance in Uganda and Malawi (DRUM) Consortium is a project that aims to transform our understanding of the drivers of AMR in Eastern Africa, and enable the design of interventions to mitigate antimicrobial resistance (AMR) spread by determining specific drivers of transmission. Using whole genome sequencing (WGS), we are characterising the emergence and spread of AMR within complex social settings in Uganda and Malawi and inputting into an agent-based model in order to understand the mechanisms that support the emergence, movement, and persistence of AMR within communities. We first performed short read WGS of ESBL producing Enterobacteriaceae (ESBL) from the DRUM project, whose analysis unravelled huge diversity of ESBL-E Enterobacteriaceae and determinants from Uganda and Malawi. However, due to limitations of short read WGS we could not fully analyse the genetic environments of AMR genes, most of which were carried on plasmids. We would like to further sequence selected genomes from this collection, but on a long-read platform to: • Understand the flux of AMR genes and the mobile genetic elements harbouring them, plasmids in particular, across lineages and ecological niches. • Generate reference genome sequences for novel lineages or lineages with no well curated reference genomes to enable lineage specific analyses and support modelling We will perform long-read sequencing on PacBio platform for 100 E. coli and Klebsiella pneumoniae isolates, which represent the major lineages of E. coli and K. pneumoniae identified during analysis of the initial single isolate WGS data.