erythromycin resistance in Aliarcobacter butzleri

Macrolides are one of the recommended antibiotic classes in the treatment of the emerging enteropathogen Aliarcobacter butzleri, nonetheless this bacterium' isolates may present highly variable resistance rates and the mechanisms behind this resistance phenotype remain mostly unexplored. In this study, resistant strains resulting from spontaneous mutations and adaptative laboratory evolution of A. butzleri under increasing concentrations of erythromycin were examined to understand the phenotypic and genotypic consequences associated with the acquisition of resistance, as well as the effects on the fitness of this species. A. butzleri clones from spontaneous mutation rate evolution demonstrated a decrease in susceptibility to erythromycin but also to other classes of antibiotics, associated with mutations in the transcriptional repressor areR that resulted in overexpression of the AreABC efflux pump. In turn, whole-genome sequencing analysis of the evolved strain showed additional mutations in the ribosomal proteins L4 and L22 and in the areR gene, which may act synergistically to give rise to high-levels of resistance to erythromycin. Furthermore, the results suggest that the acquisition of macrolide resistance altered the virulence of A. butzleri and entailed a high biological cost that may be associated with the low prevalence of high-level erythromycin-resistant strains in the environment.