AUTHOR=Abdel-Glil Mostafa Y. , Hotzel Helmut , Tomaso Herbert , Linde Jörg 

TITLE=Phylogenomic Analysis of Campylobacter fetus Reveals a Clonal Structure of Insertion Element ISCfe1 Positive Genomes

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.585374

DOI=10.3389/fmicb.2020.585374

ISSN=1664-302X

ABSTRACT=<p>Subspecies of the species <italic>Campylobacter fetus</italic> are associated with specific host niches including mammals and reptiles. <italic>Campylobacter fetus</italic> subsp. <italic>fetus</italic> is a zoonotic pathogen infecting humans. Infections can vary from an acute intestinal illness to severe systemic infections, with sheep and cattle as major reservoirs. In contrast, <italic>Campylobacter fetus</italic> subsp. <italic>venerealis</italic> causes bovine genital campylobacteriosis, which leads to abortion in cattle and a high economic burden for the farmers. Therefore, high-quality molecular subtyping is indispensable for interventional epidemiology. We used whole-genome sequencing (WGS) data of 283 <italic>Campylobacter fetus</italic> strains from 18 countries and compared several methods for <italic>Campylobacter fetus</italic> subtyping, including WGS, multilocus sequence typing, PCR assays, and the presence of the insertion element IS<italic>Cfe1</italic>. We identified a highly clonal clade (designated as clade 1) that harbors the insertion sequence IS<italic>Cfe1</italic>. The presence of this insertion sequence is an essential diagnostic tool for the identification of the subspecies <italic>Campylobacter fetus</italic> subsp. <italic>venerealis</italic>, serving as a target for several PCR assays. However, we have found a high sequence variability for the IS<italic>Cfe1</italic> besides the presence of IS<italic>Cfe1</italic>-paralogues in certain other genomes (<italic>n</italic> = 7) which may cause incorrect diagnostic results. Clade 1 seems to be the cattle-specific clade of this species. We propose that only this clade might be designated as <italic>Campylobacter fetus</italic> subsp. <italic>venerealis</italic> as it harbors the IS<italic>Cfe1</italic> marker sequence, which is a major target for molecular methods currently used for <italic>Campylobacter fetus</italic> subspecies identification. Fostering this proposal, we defined eleven stable nucleotide markers specific for this clade. Additionally, we developed a bioinformatics toolbox for the fast identification of this clade based on WGS data. In conclusion, our results demonstrate that WGS can be used for <italic>Campylobacter fetus</italic> subtyping overcoming limitations of current PCR and MLST protocols.</p>