A One Health Analysis of Bacterial and Fungal Threats
Open Access DepositedAgriculture-driven Human Infectious Diseases and Antimicrobial Resistance
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Zoonotic transmission contributed substantially to extraintestinal E. coli infections
25.5% of UTIs caused by ESBL-producing E. coli in Ecuador and 18.1% of extraintestinal infections globally were food-animal derived. Zoonotic proportions were significantly higher in low- and middle-income countries (LMICs, BSI
24.2%) than high-income countries (HICs, BSI
This dissertation provides novel empirical evidence characterizing and quantifying agriculture as a driver of two clinically significant but underappreciated human infectious diseases—extraintestinal E. coli infections and aspergillosis—and demonstrates how agricultural antimicrobial use amplifies resistance in these pathogens through parallel bacterial and fungal pathways. These results highlight the urgent need for integrated One Health surveillance, harmonized international regulatory frameworks, and evidence-based interventions addressing agricultural contributions to infectious disease and antimicrobial resistance.
Background
Modern agricultural practices create pathways through which pathogens, including antimicrobial-resistant strains, can spread to humans and cause diseases. Two such examples—extraintestinal Escherichia coli infections and aspergillosis—impose substantial global burdens, yet their agricultural drivers remain understudied. Methods
17.8%, UTI
27.0%, UTI
For bacterial investigations, an initial study analyzed 137 clinical ESBL-producing E. coli isolates from urinary tract infections (UTIs) in Ecuador, followed by an expanded global analysis of 14,585 bloodstream infection (BSI) and UTI isolates from 75 countries (1985–2022). A Bayesian latent class model leveraging host-associated mobile genetic elements was used to estimate the proportion of extraintestinal E. coli infections attributable to food-animal origins. Isolates were characterized for sequence types, antimicrobial resistance profiles, and virulence genes, with the global study stratified by country income level. For fungal investigations, 2,421 consecutive Aspergillus cultures from Kaiser Permanente Southern California (2019–2023) underwent triazole susceptibility screening. Whole-genome sequencing and minimum inhibitory concentration testing were performed on selected clinical isolates and 77 soil isolates from California vineyards and nature parks. Phylogenetic analyses enabled species-level identification and comparison of clinical and environmental strains. Triazole fungicide application patterns and soil residue concentrations were characterized to assess environmental exposure. Results
17.5%). Putative zoonotic strains in Ecuador harbored distinctive genomic signatures including ColV virulence genes and animal-associated β-lactamase genes. Globally, isolates from LMICs exhibited greater multidrug resistance than isolates from HICs. Aspergillus tubingensis was identified as a prevalent yet systematically misidentified pathogen, comprising more than two-thirds of clinical A. niger complex isolates in Southern California. Triazole resistance was widespread, with 15.1% of isolates growing at epidemiological cut-offs. Environmental sampling revealed that A. tubingensis was commonly isolated from California environments, with clinical and environmental isolates clustering phylogenetically, suggesting environmental transmission. This finding aligned with widespread triazole fungicide application in California agriculture, where residues were detected in vineyard soils. Conclusion
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