Global transcriptional response of Acinetobacter baumannii to a subinhibitory concentration of tigecycline.

Acinetobacter baumannii has emerged as a significant nosocomial pathogen worldwide. Multidrug resistance has limited the treatment options for A. baumannii. Tigecycline belongs to a new class of modified tetracycline antimicrobials known as glycylcyclines and has demonstrated good in vitro antimicrobial activity against multidrug-resistant Acinetobacter spp. However, tigecycline-resistant strains may be generated during treatment. To explore the response to tigecycline in A. baumannii, the transcriptional profile of A. baumannii was determined in the presence and absence of tigecycline. The results showed that a major facilitator superfamily (MFS) efflux pump and multiple transcriptional regulators possibly involved in the stress response and drug resistance were upregulated in response to tigecycline. Strong suppressors in the aerobic phenylacetate catabolic pathway and a number of ATP-binding cassette (ABC) transporters were also observed after exposure to tigecycline. Furthermore, A. baumannii showed a lower minimum inhibitory concentration of ceftazidime in the presence of tigecycline owing to downregulated OXA-23 and AmpC. These finding suggest that the response of A. baumannii to tigecycline is multifactorial and includes MFS family efflux pump transcriptional regulators and metabolic pathways, such as the phenylacetate catabolic pathway.