Unraveling virulence determinants in extended-spectrum beta-lactamase-producing Escherichia coli from East Africa using whole-genome sequencing

Ivan Sserwadda; Benson R Kidenya; Stephen Kanyerezi; Inyasi Lawrence Akaro; Baraka Mkinze; Stephen E Mshana; Suhaila O Hashim; Everlyne Isoe; Jeremiah Seni; Moses L Joloba; Gerald Mboowa

doi:10.1186/s12879-023-08579-0

Unraveling virulence determinants in extended-spectrum beta-lactamase-producing Escherichia coli from East Africa using whole-genome sequencing

BMC Infect Dis. 2023 Sep 7;23(1):587. doi: 10.1186/s12879-023-08579-0.

Authors

Ivan Sserwadda^#^{1

2

3}, Benson R Kidenya^#⁴, Stephen Kanyerezi^{1

3}, Inyasi Lawrence Akaro⁵, Baraka Mkinze⁵, Stephen E Mshana⁶, Suhaila O Hashim², Everlyne Isoe², Jeremiah Seni⁶, Moses L Joloba¹, Gerald Mboowa^{7

8

9}

Affiliations

¹ Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O Box 7072, Kampala, Uganda.
² Department of Biochemistry and Bioinformatics, School of Pure and Applied Sciences, Pwani University, P.O Box 195-80108, Kilifi, Kenya.
³ The African Center of Excellence in Bioinformatics and Data-Intensive Sciences, Infectious Diseases Institute, College of Health Sciences, Makerere University, P.O Box 22418, Kampala, Uganda.
⁴ Department of Biochemistry and Molecular Biology, Weill Bugando School of Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
⁵ Department of Surgery, Weill Bugando School of Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
⁶ Department of Microbiology and Immunology, Weill Bugando School of Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
⁷ Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O Box 7072, Kampala, Uganda. gmboowa@gmail.com.
⁸ The African Center of Excellence in Bioinformatics and Data-Intensive Sciences, Infectious Diseases Institute, College of Health Sciences, Makerere University, P.O Box 22418, Kampala, Uganda. gmboowa@gmail.com.
⁹ Africa Centres for Disease Control and Prevention, African Union Commission, Roosevelt Street, P.O. Box 3243, Addis Ababa, W21 K19, Ethiopia. gmboowa@gmail.com.

^# Contributed equally.

Abstract

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 .

Keywords: Antimicrobial resistance; East Africa; Extended-spectrum β-lactamase; Virulence factors; Whole-genome sequencing.

MeSH terms

Chloramphenicol
Enterotoxigenic Escherichia coli*
Humans
Longitudinal Studies
Uganda / epidemiology
Virulence
beta-Lactamases / genetics

Substances

Chloramphenicol
beta-Lactamases

Abstract

MeSH terms

Substances

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