Whole strains vs MGEs in short and longterm transmission of ESBL genes between healthcare and community settings in Uganda

Abstract

Multidrug-resistant ESBL-producing Escherichia coli are a leading cause of infections in hospital and community settings. Based on samples from two hospitals in Uganda and households of inpatients we tested the hypothesis that ESBL E. coli and/or their resistance determinants could spread within the healthcare and community settings through discharged patients that were still colonized. We used bacterial culture, susceptibility testing whole genome sequencing and detailed bioinformatics analysis to test the above hypothesis. Genome analysis revealed presence of predominantly blaCTX-M-15 and blaOXA-1 genes with a total resistome with genes belonging to 14 different classes of antimicrobials. Short-term cases of strain sharing were reported within each setting and strains from the two settings were found to cluster together based on their overall resistome. Long-term horizontal transfer of ESBL genes by various IncF and IncY types of plasmids shared between healthcare and community settings was demonstrated. Based on hybrid assembly, plasmid reconstruction and phylogenetic analyses, our study suggests that while the dissemination of AMR between healthcare and community settings in the short-term is possible at whole strain level, the long-term transmission between healthcare and communities is sustained by the transfer of plasmids circulating across niches and disseminating related resistomes.

Genome Analysis of Klebsiella pneumoniae Reveals International High-Risk Pandemic MDR Clones Emerging in Tertiary Healthcare Settings in Uganda

“…The fact that all our isolates, except three, carried plasmids signifies a serious problem, especially within healthcare settings, and calls for more dedicated infection control measures to eliminate them from such facilities. Our previous studies have indeed demonstrated a higher prevalence of resistance in E. coli from healthcare environments but also from healthcare workers who may be serving as sources of infection with resistant bacteria to hospitalized patients [16].…”

“…The isolates were subjected to antimicrobial susceptibility testing against 17 antibiotics by disc diffusion assay as previously described [16] on Mueller-Hinton agar (MHA) (Oxoid, Manchester, UK). A suspension of 0.5 McFarland standard turbidity was spread on the surface of MHA plates using a sterile cotton swab.…”

Genetic Analyses of Rare ESBL ST628 Klebsiella pneumoniae Detected during a Protracted Nosocomial Outbreak in the United Kingdom

“…A CTX-M-15 encoding 180-kb IncFIIK plasmid in K. pneumoniae ST17 has been stably maintained for up to 2 years in colonised patients [38]. Furthermore, a recent study has demonstrated the long-term transmission of AMR, including ESBL genes, between healthcare and community networks can be facilitated by the transmission of plasmids circulating across niches [39]. High colonisation rates, combined with long-term persistence and plasmid transfer, may engender a scenario for future dissemination of ST628 and its CTX-M-15 encoding plasmid.…”