Antimicrobial resistance in Campylobacter fetus: emergence and transmission

Campylobacter fetus is an important pathogen for both humans and animals, but it is unknown how serious concerning antimicrobial resistance development is in C. fetus. In this study, whole genome sequences of 295 C. fetus strains isolated from 1945 to 2019 were collected and analysed for resistance genes to assess the genomic basis of resistance to antimicrobial agents in C. fetus strains. Substitutions in the chromosomal DNA gyrase appeared in the 60ths in C. fetus ovine isolates, and three gyrA substitutions (D91N, D91Y and T87I) conferring ciprofloxacin resistance were identified, whereas gyrA substitutions A14V, A14V/T and D91E were identified as silent substitutions. Resistance genes were only found in C. fetus subspecies fetus strains (n=27), mainly isolated from human cases (n=23) and earliest resistance were a tetracycline and aminoglycoside resistance gene identified in a bovine strain isolated in 1999 in Germany, and from then, the emergence of AMR in C. fetus is increasing. Resistance genes causing phenotypic tetracycline (tet(44)) and streptomycin (ant(6)) resistance were found on chromosomal islands of 12 strains, and genes causing phenotypic tetracycline (tet(O)), kanamycin (aph(3')-III) and neomycin (aph(3')-III) resistance were found to be located both on chromosomal islands and in plasmids, whereas a chloramphenicol (cat) gene was only found in a plasmid. Plasmids harboring tetracycline and aminoglycoside resistance genes are most likely shared with other Campylobacter species given their gene homology. Naladixic acid resistance was confirmed as an intrinsic resistance of C. fetus strains as all isolates were resistant.