Antibiotic resistance in Campylobacter jejuni: Molecular mechanisms, dynamics of emergence, and ecological fitness in poultry

Understanding the mechanisms of antibiotic resistance and the dynamics of emergence of resistant Campylobacter will facilitate the design of means to prevent and treat campylobacteriosis. In the first part of this study, a small plasmid (pCJ01) in an ampicillin-resistant C. jejuni strain isolated from poultry was sequenced using inverse PCR and DNA sequencing. pCJ01 is a circular molecular of 3212 base pair (bp) with typical replication origin and four predicated open reading frames (ORFs). ORF1 and ORF2 are putative RepA and RepB proteins, while ORF3 and ORF4 do not exhibit homology with any sequences deposited in the GenBank database. Despite the fact that no known resistant genes exist: in pCJ01, this plasmid may be modified for use in molecular characterization of functionally important C. jejuni genes.; In the second part of this study, the dynamics of changes in Campylobacter populations in response to the treatment with fluoroquinolone (FQ) were determined. Our work revealed the prompt disappearance of FQ-sensitive campylobacters and the quick emergence of resistant mutants in the FQ treated birds. Molecular analysis of the resistant mutants demonstrated that the acquired FQ resistance is mediated by the synergistic action of gyrA mutations and the CmeABC efflux pump.; In the third part of this study, the ecological fitness of the in vivo selected FQ-resistant C. jejuni in the absence of antibiotic selection pressure was examined using in vitro and in vivo systems. In culture media, FQ-sensitive Campylobacter is better fit than the isogenic FQ-resistant strain. However, the FQ-resistant strain has a fitness advantage in chickens even in the absence of antibiotics selection pressure.; Together, the findings demonstrate the hypermutability of C. jejuni to antibiotic treatment and highlight the need for the prudent use of FQ antibiotics in poultry production. These findings also open new avenues for future studies to prevent the occurrence of FQ-resistant C. jejuni in animal reservoirs and humans.