Longitudinal analysis of Campylobacter jejuni fluoroquinolone resistance amongst UK human disease isolates.

Abstract P8

Presenter: Dessislava Veltcheva (University of Oxford)

Authors: Dessislava Veltcheva+, Frances Colles+, Michael Bonsall, Martin Maiden (University of Oxford)

Campylobacter is a common foodborne bacterial pathogen and can cause gastroenteritis in humans. This organism is also on the watch list for increasing resistance to antibiotics on the 2019 AR Threats Report from the CDC. As a zoonotic organism, it can be isolated from a broad range of animal reservoirs and can infect humans from contaminated food, water, and milk. Campylobacter jejuni accounts for about 90% of human Campylobacteriosis cases, and Campylobacter coli accounts for most of the rest. Campylobacter is frequently exposed to antibiotics, especially in animal production. Fluoroquinolones are widely used therapeutically and additionally as growth promotors in some countries outside of the EU. Campylobacteriosis is usually a self-limiting disease in humans, but antibiotics such as macrolides may be used where patients are very young, elderly, or immunocompromised. Fluoroquinolone resistance occurs spontaneously and is most associated with the Thr86-to-Ile mutation in the gyrA gene. With no apparent fitness cost to the bacterium, susceptible populations may quickly be outcompeted, and the likelihood that growing fluoroquinolone resistance levels may be reversed is slim. Thus, antibiotic-resistant strains are a threat throughout the whole food chain, including humans as the end consumer. The study aimed to determine patterns of C. jejuni fluoroquinolone resistance amongst human disease isolates over 20 years. A total of 10,362 UK human stool isolates recorded on the PubMLST database (https://pubmlst.org/) between 1998 to 2018 were analysed. Fluoroquinolone resistance profiles were inferred from genotype data, with previous studies showing that such predictions are 98% correct. Analyses were performed using PubMLST database, R, Python, HPC, and outputs visualised in R and Tableau. Linear regression analysis indicated that C. jejuni had become increasingly resistant to fluoroquinolones over time, in line with other studies. However, when considering the distribution of resistance across clonal complexes (closely related groups of C. jejuni sequence types), three resistance patterns emerged. One group of clonal complexes showed increasing fluoroquinolone resistance over time; the second group of clonal complexes showed consistently high resistance levels over time, and the third group of clonal complexes showed consistently low levels of resistance. Three clonal complexes, CC354, 464 and 353, with high levels of fluoroquinolone resistance are typically associated with poultry sources. In contrast, CC61 associated with cattle was susceptible. These results demonstrate the importance of understanding C. jejuni population structures, with all strains not being equal in the rise of fluoroquinolone resistance. We are still seeing evidence of increasing fluoroquinolone resistance in some C. jejuni lineages beyond the EU ban of growth-promoting antibiotics in 2006.

About the presenter

My name is Dessislava Veltcheva (Dessi), and I am a third-year PhD student at the University of Oxford in the Zoology department. I am co-supervised by Professor Michael Bonsall and Professor Martin Maiden. My PhD looks at the dynamics of fluoroquinolone resistance in Campylobacter jejuni using data science, bioinformatics, phylogenetics, and machine learning. I am looking at the fluoroquinolone resistance in the food chain, longitudinal analysis, genotype to phenotype prediction and pattern recognition in the strain dynamics. Before my PhD, I gained an MSc in Bioinformatics and Systems Biology from the University of Manchester. I worked on the 100,000 genome project and created pipelines to investigate genetic components of eye diseases. Before this, I completed a BSc in Bioarchaeology from the University of York. I studied 9500 years old Jomon period Japanese potteries using lipid residue analysis to understand the ancient diet. I love science communication and public outreach, and I am a co-founder of the Chicken Journal Club (CJC): https://linktr.ee/chickenjclub. We are a multinational and multidisciplinary group from more than ten countries across all six continents composed of over a hundred and sixty graduate-level early career researchers (ECRs), and global leaders in their field. During the COVID-19 pandemic, we created an international online community that gathers international researchers to discuss their work across various disciplines on a term basis via Zoom Cloud Meetings. Social media has been a significant keystone to building our community, with our Twitter account as the main protagonist from the inception of the CJC, helping communicate updates, events and research outputs from members. Recognising the challenges of globalisation, with the many international time zone differences, our Youtube channel serves as a repository of most recorded sessions.

Presenting in Speaking session 2 - Pathogenesis