Overexpression of AdeABC efflux pump associated with tigecycline resistance in clinical Acinetobacter nosocomialis isolates

Abstract

ObjectivesTigecycline non-susceptible Acinetobacter nosocomialis (TNAN) has been discovered in clinical isolates. The resistance-nodulation-cell division (RND)-type efflux system plays a major role in tigecycline non-susceptible Acinetobacter baumannii, but the mechanism in A. nosocomialis remains unknown. Our aim was to analyse the contribution of efflux-based tigecycline resistance in clinical A. nosocomialis isolates collected from multiple medical centres in Taiwan. MethodsA total of 57 A. nosocomialis isolates, including 46 TNAN and 11 tigecycline-susceptible A. nosocomialis (TSAN) isolates, were analysed. Of these, 46 TNAN isolates were clustered to ST410 (43 isolates) and ST68 (three isolates) by multi-locus sequence typing. ResultsThe relationship between the RND efflux pump and tigecycline resistance was indirectly verified by successfully reducing tigecycline resistance with NMP, an efflux pump inhibitor. The three RND efflux systems (AdeABC, AdeIJK and AdeFGH) were detected in all clinical isolates. The transcript level of adeB gene increased significantly and was correlated with tigecycline resistance. Moreover, the AdeRS two-component system was further classified into four different types of AdeRS patterns considering the amino acid sequence. Further analysis showed that tigecycline resistance was related to the transcript level of adeB gene and the AdeRS pattern. ConclusionThis study showed that the dissemination of TNAN isolates in Taiwan is attributable mainly to the spread of ST410. The AdeABC efflux pump appeared to play an important role in the tigecycline resistance of A. nosocomialis.