A One Health genomic approach to Escherichia coli clonality and antimicrobial resistance from Bangladesh

Thesis

Antimicrobial resistance (AMR) in Escherichia coli represents a critical global health challenge, particularly in low- and middle-income countries where extensive antibiotic use and abuse in human medicine, livestock farming, and environmental contamination accelerates the spread of AMR. In Bangladesh, where population density, poor sanitation and waste management practices provide favourable conditions for the dissemination of AMR bacteria, systematic genomic studies on E. coli across interconnected sources remain scarce. This thesis characterises the genomic diversity, resistance mechanisms, and virulence potential of E. coli at the human–animal–environment interface within a One Health framework and examines the role of horizontal gene transfer in the dissemination of clinically significant resistance genes.

A One Health sampling strategy (Chapter 3) captured E. coli from clinical patients, healthy volunteers, poultry, domestic animals, and environmental sources, establishing a multi-sectoral dataset to evaluate transmission dynamics. Phenotypic susceptibility testing against 17 clinically important antibiotics revealed high-levels of resistance to β-lactams, aminoglycosides, and fluoroquinolones (Chapter 4).

Genomic analyses demonstrated extensive clonal diversity, with several globally recognised high-risk sequence types (ST131, ST410, ST648, and ST1193) detected across reservoirs (Chapter 5). Phylogroup distributions overlapped between human and non-human sources, underscoring potential cross-reservoir transmission. AMR was predominantly mediated by blaCTX-M-15, blaNDM-5, qnrS1, and genes conferring resistance to aminoglycosides. Virulence profiling revealed widespread presence of extra-intestinal pathogenic E. coli-associated determinants, often co-localising with AMR genes.

A key finding was the detection of the plasmid-mediated tet(X4) gene, conferring tigecycline resistance, and carbapenem resistance mediated by blaNDM-5. Plasmid characterisation and genomic context analyses (Chapter 6) confirmed that both genes were disseminated via horizontal gene transfer across diverse clonal backgrounds, highlighting the risk of mobile resistance elements in amplifying AMR.

These findings demonstrate the extensive genomic diversity and AMR burden of E. coli circulating in Bangladesh and emphasise the critical role of horizontal gene transfer in the emergence of resistance to last-resort antibiotics. This thesis provides the first comprehensive One Health genomic snapshot of E. coli in Bangladesh and delivers essential baseline evidence to support integrated AMR interventions and stewardship strategies at national and global levels.

Authors: Pondit, A

• DOI: 10.5287/ora-dxgko6mky
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: multidrug resistance; One Health; genomic epidemiology; escherichia coli; antimicrobial resistance in Bangladesh; antimicrobial resistance (AMR)
• Subjects: Microbiology; Escherichia coli; Multidrug resistance; Drug resistance in microorganisms