Pan-resistome characterization of uropathogenic Escherichia coli and Klebsiella pneumoniae strains circulating in Uganda and Kenya isolated from 2017-2018

Background Urinary tract infection (UTI) develops after a pathogen adhered to the inner lining of the urinary tract. Cases of UTIs are predominantly caused by several Gram-negative bacteria and account for high morbidity in the clinical and community settings. Of greater concern are the strains carrying antimicrobial resistance (AMR)-conferring genes. The gravity of UTI is also determined by a spectrum of other virulence factors. This study represents a pilot project to investigate the burden of AMR among uropathogens in East Africa. Methods We examined bacterial samples isolated in 2017-2018 from in- and out-patients in Kenya (KY) and Uganda (UG) that presented with clinical symptoms of UTI. We reconstructed the evolutionary history of the strains, investigated their population structure and performed comparitive analysis their pangenome contents. Results We found 55 Escherichia coli and 19 Klebsiella pneumoniae strains confirmed uropathogenic following screening for the prevalence of UTI virulence genes including fimH, iutA, feoA / B / C, mrkD and foc . We identified 18 different sequence types in E. coli population while all K. pneumoniae strains belong to ST11. The most prevalent E. coli sequence types were ST131 (26%), ST335/1193 (10%) and ST10 (6%). Diverse plasmid types were observed in both collections such as Incompatibility (IncF/IncH/IncQ1/IncX4) and Col groups. Pangenome analysis of each set revealed a total of 2,862 and 3,464 genes comprised the core genome of E. coli and K. pneumoniae population, respectively. Among these are AMR determinants including fluoroquinolone resistance-conferring genes aac (3 )-Ib-cr and other significant genes: aad, tet, sul1, sul2 , and cat , which are associated with aminoglycoside, tetracycline, sulfonamide and chloramphenicol resistance. Accessory genomes of both species collection were detected several β-lactamase genes, bla CTX-M , bla TEM and bla OXA or bla NDM . Overall, 93% are multi-drug resistant in the E. coli collection while 100% of the K. pneumoniae strains contained genes that are associated with resistance to 3 or more antibiotic classes. Conclusions Our findings illustrate the abundant resistome and virulome repertoire in uropathogenic E. coli and K. pneumoniae , which are mainly disseminated via clonal and horizontal transfer, circulating in the East African region. We further demonstrate here that routine genomic surveillance is necessary for high-resolution bacterial epidemiology of these important AMR pathogens.