TY - JOUR
T1 - Unraveling virulence determinants in extended-spectrum beta-lactamase-producing Escherichia coli from East Africa using whole-genome sequencing
AU - Sserwadda, Ivan
AU - Kidenya, Benson R.
AU - Kanyerezi, Stephen
AU - Akaro, Inyasi Lawrence
AU - Mkinze, Baraka
AU - Mshana, Stephen E.
AU - Hashim, Suhaila O.
AU - Isoe, Everlyne
AU - Seni, Jeremiah
AU - Joloba, Moses L.
AU - Mboowa, Gerald
N1 - Funding Information: We are equally grateful for the support of the NIH Common Fund, through the OD/Office of Strategic Coordination (OSC) and the Fogarty International Center (FIC), NIH award number U2RTW010672. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the supporting offices”. Funding Information: This study was part of the research project titled, “Understanding transmission dynamics and acquisition of antimicrobial resistance at referral hospitals and community settings in East Africa”, supported through the Grand Challenges (GC) Africa programme (Grant number GCA/AMR/rnd2/058). The GC Africa is a programme of the African Academy of Sciences (AAS) implemented through the Alliance for Accelerating Excellence in Science in Africa (AESA) platform, an initiative of the AAS and the African Union Development Agency(AUDA-NEPAD). The GC Africa is supported by the Bill and Melinda Gates Foundation (BMGF) and the African Academy of Sciences and partners. It was executed collaboratively between Makerere University College of Health Sciences, Kampala, Uganda, and the Catholic University of Health and Allied Sciences, Mwanza, Tanzania. The funders had no roles in the design, execution, data management, manuscript writing, or manuscript submission. This work was also in part supported by the African Association for Research and Control of Antimicrobial Resistance (AAAMR) 2020 Young Anglophone Investigator Award to G.M and the Public Health Alliance for Genomic Epidemiology (PHA4GE) Grant (INV-038071) to support pathogen genomics data standards and bioinformatics interoperability awarded to I.S. Funding Information: Ivan Sserwadda is a fellow of the Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) program. He is also supported by MUII. MUII is supported through the DELTAS Africa Initiative (Grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK Government. Funding Information: Ivan Sserwadda is a fellow of the Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) program. He is also supported by MUII. MUII is supported through the DELTAS Africa Initiative (Grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK Government. We are equally grateful for the support of the NIH Common Fund, through the OD/Office of Strategic Coordination (OSC) and the Fogarty International Center (FIC), NIH award number U2RTW010672. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the supporting offices”. Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum β-lactamase (ESBL)-producing E. coli from African clinical settings. This hospital-based longitudinal study unraveled the genetic resistance elements in ESBL E. coli isolates from Uganda and Tanzania using whole-genome sequencing (WGS). A total of 142 ESBL multi-drug resistant E. coli bacterial isolates from both Tanzania and Uganda were sequenced and out of these, 36/57 (63.1%) and 67/85 (78.8%) originated from Uganda and Tanzania respectively. Mutations in RarD, yaaA and ybgl conferring resistances to chloramphenicol, peroxidase and quinolones were observed from Ugandan and Tanzanian isolates. We reported very high frequencies for bla CTX−M−15 with 11/18(61.1%), and bla CTX−M−27 with 12/23 (52.1%), bla TEM−1B with 13/23 (56.5%) of isolates originating from Uganda and Tanzania respectively all conferring resistance to Beta-lactam-penicillin inhibitors. We observed chloramphenicol resistance-conferring gene mdfA in 21/23 (91.3%) of Tanzanian isolates. Extraintestinal E. coli sequence type (ST) 131 accounted for 5/59 (8.4%) of Tanzanian isolates while enterotoxigenic E. coli ST656 was reported in 9/34 (26.4%) of Ugandan isolates. Virulence factors originating from Shigella dysenteriae Sd197 (gspC, gspD, gspE, gspF, gspG, gspF, gspH, gspI), Yersinia pestis CO92 (irp1, ybtU, ybtX, iucA), Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (csgF and csgG), and Pseudomonas aeruginosa PAO1 (flhA, fliG, fliM) were identified in these isolates. Overall, this study highlights a concerning prevalence and diversity of AMR-conferring elements shaping the genomic structure of multi-drug resistant E. coli in clinical settings in East Africa. It underscores the urgent need to strengthen infection-prevention controls and advocate for the routine use of WGS in national AMR surveillance and monitoring programs. Availability of WGS analysis pipeline: the rMAP source codes, installation, and implementation manual can free be accessed via https://github.com/GunzIvan28/rMAP .
AB - Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum β-lactamase (ESBL)-producing E. coli from African clinical settings. This hospital-based longitudinal study unraveled the genetic resistance elements in ESBL E. coli isolates from Uganda and Tanzania using whole-genome sequencing (WGS). A total of 142 ESBL multi-drug resistant E. coli bacterial isolates from both Tanzania and Uganda were sequenced and out of these, 36/57 (63.1%) and 67/85 (78.8%) originated from Uganda and Tanzania respectively. Mutations in RarD, yaaA and ybgl conferring resistances to chloramphenicol, peroxidase and quinolones were observed from Ugandan and Tanzanian isolates. We reported very high frequencies for bla CTX−M−15 with 11/18(61.1%), and bla CTX−M−27 with 12/23 (52.1%), bla TEM−1B with 13/23 (56.5%) of isolates originating from Uganda and Tanzania respectively all conferring resistance to Beta-lactam-penicillin inhibitors. We observed chloramphenicol resistance-conferring gene mdfA in 21/23 (91.3%) of Tanzanian isolates. Extraintestinal E. coli sequence type (ST) 131 accounted for 5/59 (8.4%) of Tanzanian isolates while enterotoxigenic E. coli ST656 was reported in 9/34 (26.4%) of Ugandan isolates. Virulence factors originating from Shigella dysenteriae Sd197 (gspC, gspD, gspE, gspF, gspG, gspF, gspH, gspI), Yersinia pestis CO92 (irp1, ybtU, ybtX, iucA), Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (csgF and csgG), and Pseudomonas aeruginosa PAO1 (flhA, fliG, fliM) were identified in these isolates. Overall, this study highlights a concerning prevalence and diversity of AMR-conferring elements shaping the genomic structure of multi-drug resistant E. coli in clinical settings in East Africa. It underscores the urgent need to strengthen infection-prevention controls and advocate for the routine use of WGS in national AMR surveillance and monitoring programs. Availability of WGS analysis pipeline: the rMAP source codes, installation, and implementation manual can free be accessed via https://github.com/GunzIvan28/rMAP .
KW - Antimicrobial resistance
KW - East Africa
KW - Extended-spectrum β-lactamase
KW - Virulence factors
KW - Whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85170156012&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12879-023-08579-0
DO - https://doi.org/10.1186/s12879-023-08579-0
M3 - Article
C2 - 37679664
SN - 1471-2334
VL - 23
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 587
ER -