Impact of erythromycin resistance on the virulence properties and fitness of Campylobacter jejuni

Abstract

Epidemiological studies of macrolide resistance in Campylobacter jejuni demonstrated that infections with macrolide-resistant C. jejuni could be associated with an increased risk of adverse events, development of invasive illness or death compared to macrolide-susceptible isolates. In this study, an in vitro induction experiment was conducted using susceptible C. jejuni strain and erythromycin as a selecting agent to obtain Ery-resistant mutant with 23S rRNA gene mutation (A2074C). Changes in the virulence characteristics and fitness between the susceptible parent strain and Ery-resistant mutant were examined. Ery-resistant mutant demonstrated slightly more resistance to bile in the bile tolerance assay compared to the susceptible strain but with no statistical significant difference. However Ery-resistant mutant apparently demonstrated reduced adhesion and invasion characteristics to intestinal epithelial cells, murine macrophage and short time intracellular survivability within macrophage compared to the susceptible strain. Co-inoculation of the two strains in the mice resulted in low colonization level of the resistant strain compared to the susceptible strain. Competition experiments resulted in mutant that grew significantly slower than the susceptible parent strain and the mutation imposed a fitness cost in Ery-resistant mutant. Taken together these findings demonstrated the increment of the virulence characteristics of Ery-susceptible strain rather than Ery-resistant strain. The adverse events previously observed in the epidemiological studies for macrolide-resistant strains infection, we suggested this maybe attributed to the resistivity of the resistant strains to the treatment and consequently prolonged the symptoms and compromised the disease in patients.