A-031. Role of the HefA Efflux System in Antimicrobial Resistance of Helicobacter hepaticus

C. Belzer1, S. Breijer1, J. G. Kusters1, E. J. Kuipers1, A. H. M. van Vliet2,1;
1Erasmus MC, Rotterdam, THE NETHERLANDS, 2Inst. of Food Res., Norwich, UNITED KINGDOM.

Helicobacter species colonize the gastrointestinal and hepatobiliary tract of mammals, and often cause inflammation-associated diseases. Antibiotic treatment of a gastric Helicobacter infection consists of Bismuth-based quadruple therapy or PPI-based triple therapy with amoxicillin and levofloxacin. Although, this treatment may be effective for the eradication of H. pylori, not much is known about antibiotic susceptibility of other Helicobacter species. We have tested a range of gastric and enterohepatic Helicobacter species for their susceptibility to a range of antimicrobial compounds. The gastric Helicobacter species were all susceptible to amoxicillin (MIC values of 0.047, <0.016, and 0.25 mg/L for H. pylori, H. mustelae and H. acinonychis respectively). Wild-type strains of the enterohepatic Helicobacter species (H. hepaticus, H. bilis and H. rappini) were all resistant to amoxicillin (MIC values of 64, 16 and 8 mg/L respectively). Mutational studies with the highly resistant H. hepaticus demonstrated that the HefA component of the HefABC RND-efflux system is involved in amoxicillin resistance as disruption resulted in loss of amoxicillin resistance (MIC 0.25 mg/L). HefA disruption was also associates with increased sensitivity to the bile acids; cholic acid and deoxycholic acid. Furthermore, transcription of the hefA gene was induced by bile acids, but was not affected by amoxicillin supplementation. Rodents are the natural hosts of enterohepatic Helicobacter species. It is conceivable that this colonization affects the global health status and immune response of these animals and for this reason animal facilities have test and treat strategies for these putative pathogens. Our finding that enterohepatic Helicobacter species can be naturally resistant against amoxicillin should be considered in eradication programs of animal facilities worldwide.