Dissertation: Extended-Spectrum Beta-Lactamase-producing Enterobacteriaceae through the lens of One Health in the Whole Genome Sequencing Era
Extended-spectrum beta-lactamase-producing Enterobacteriaceae are found in humans, animals, and the environment. The global spread of antimicrobial resistance demands for cross-sectional research to determine different transmission routes. Whole genome sequencing is a powerful tool to study the similarities between resistant bacteria and plasmids harboring resistance genes.

Paula Kurittu, DVM, defended her PhD thesis on September 30th, 2022. The opponent was Adjunct Professor Antti Hakanen, Univeristy of Turku, and the custos Professor Maria Fredriksson-Ahomaa, University of Helsinki.

In her thesis Kurittu studied the occurrence and epidemiology of ESBL/AmpC-producing Enterobacteriaceae in different sources in Finland including broiler production, food products, migratory birds, and human clinical samples. Using whole genome sequencing, bacterial strains were characterized and compared to bacterial strains and plasmids from global databases to discover potential successful plasmids and resistance genes and bacterial sequence types.

Extended-spectrum beta-lactamase (ESBL/AmpC) producing Enterobacteriaceae, especially Escherichia coli and Klebsiella pneumoniae, are one of the most important bacteria resistant to commonly used antibiotics. These bacteria are found in humans, animals, and the environment. Antimicrobial resistance genes are often located on mobile genetic elements, plasmids, which has enabled their global spread.

Poultry and broiler meat have been recognized as a reservoir for ESBL/AmpC- producing E. coli worldwide. In Finland, antibiotics have not been used in broiler production for over a decade, but nevertheless ESBL/AmpC-producing bacteria have been discovered in the production chain. To study the occurrence and transmission routes of ESBL/AmpC-producing E. coli in the broiler production pyramid, samples were taken from different stages of the production pyramid. ESBL/AmpC-producing E. coli was detected in 26.7% of parent level birds, but ESBL/AmpC-producing E. coli was absent from egg surfaces after an incubation period at a hatchery, and E. coli was very rare in hatchlings (2.2%). The findings indicate the transmission routes of these bacteria in the production pyramid are a combination of horizontal and vertical routes, rather than strictly vertical.

In the second study fecal samples were collected from barnacle geese. A rare multireplicon plasmid was identified from E. coli, indicating the adaptive nature of plasmids harboring resistance genes. ESBL/AmpC-producing E. coli was found in 4.5% of the barnacle goose fecal samples. 

In a study conducted in collaboration with the Finnish Food Authority and the Customs Laboratory, investigating the occurrence of ESBL/AmpC-producing E. coli and K. pneumoniae in global food products demonstrated raw broiler meat as a potential source for these resistant bacteria. ESBL genes, such as blaCTX-M-15, were recognized in certain food products together with human-associated K. pneumoniae multilocus sequence types, indicating a possible human-related source of transmission.

Study of ESBL-producing E. coli isolates from human patients in eastern Finland with WGS identified blaCTX-M-27 as the most common ESBL gene. Core genome multilocus sequence typing and comparison of the isolates suggested human-derived ESBL-producing E. coli isolates are distinct from ESBL/AmpC-producing E. coli isolates obtained from animal, food, and environmental sources in Finland. The ever-evolving global health pandemic of AMR demands for a combined effort of different sectors and continuous monitoring, in which WGS has proved to be invaluable.

The research received funding from the Academy of Finland, the Walter Ehrström Foundation, the Finnish Foundation of Veterinary Research, the Finnish Food Research Foundation, European Union's Horizon 2020 Research and Innovation Program, the Doctoral Program in Food Chain and Health, and the Doctoral School in Environmental, Food and Biological Sciences. The funders are gratefully acknowledged for financially supporting the thesis.

 Digital version of the PhD thesis