Adaptive responses of campylobacter jejuni to antibiotic and biocide selection pressures in chemostat culture
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Campylobacter jejuni (C. jejuni) is a zoonotic pathogen of major public health importance and is the leading cause of gastroenteritis woldwide. Poultry is regarded as one of the most important reservoirs for Campylobacter and constitutes a very significant vehicle for the transmission of Campylobacter to humans. Prevention measures including biosecurity and good hygiene practices (relying on the use of disinfectant) are widely used to prevent the transmission of Campylobacter to poultry. Benzalkonium chloride (BKC) a quaternary ammonium compound is commonly used disinfectant in the poultry industry. Fluoroquinolones are one of the main antibiotic classes used in the treatment of Campylobacter infections. Resistance to fluroquinolones in Campylobacter is rising in recent years and has been linked to their use in animal husbandry. Campylobacter jejuni NCTC 11168 was adapted to ciprofloxacin and BKC following long-term exposure in chemostat culture. Chemostat-adapted variants reduced susceptibility to ciprofloxacin (1,028-fold) and BKC (8-fold) were characterized. Adapted variants were less fit than their un-adapted counterpart and showed stable reduced susceptibility after prolonged culture. Strain- specific differences in efflux activity and cross-resistance profiles to other antimicrobials were observed for ciprofloxacin-adapted variants. Similarly the development of low-level cross-resistance to ciprofloxacin and cefotaxime found in BKC-adapted variants. Efficacy of the commercial disinfectant SavlonTM against adapted variants was also reduced but not at recommended use concentrations. Mutations and proteomic changes in proteins involved in metabolism and the general stress response were associated with high-level ciprofloxacin-resistant variants while changes in oxidative stress proteins were found in BKC-adapted variants. This thesis provides further insights into the development of antimicrobial resistance in Campylobacter.