Genomic comparison of highly related pairs of E. coli and K. pneumoniae isolated from faeces and blood of the same neonatal patients hospitalized with fever in Dar es Salaam, Tanzania

Blood stream infections (BSIs) are a major cause of hospitalisation and death for children under the age of five in sub-Saharan Africa with members of the Gram-negative bacteria Enterobacterales such as Klebsiella pneumoniae and Escherichia coli among the most common causative agents. These bacteria usually colonise the human gastrointestinal (GI) tract which has been identified as a reservoir for invasive infections into extra-intestinal environments such as the urinary tract and bloodstream. In this study we used comparative genomics to compare hybrid genome assemblies of blood and faecal isolates taken from the same patients (all neonates under 19 days old) to determine if the BSI associated bacterial isolates originated in their GI tract. We show that both E. coli and K. pneumoniae likely translocated from the GI tract to the blood in multiple cases of BSI. We also highlight key virulence genes and acquired mutations that are indicative of pathogenic strains capable of BSI. These findings expand our understanding of BSI pathogenesis and could help guide targeted interventions to prevent future BSI infections in neonates.