baumannii isolates collected from 21 medical centers and regional hospitals were ceftazidime-resistant [4]. Therefore, there are only a few effective anti-Acinetobacter

drugs currently available, including polymyxins and tigecycline [5]. Tigecycline is the first drug from the glycylcycline class, a new class of antibiotics derived from tetracycline [6]. Tigecycline acts as a protein synthesis inhibitor by binding to the 30S ribosomal subunit, and thus blocking entry of the tRNA into the A site of the ribosome during translation. Although tigecycline has an expanded spectrum of antibacterial activity, previous studies have shown that tigecycline resistance has emerged in A. baumannii. Resistance in these strains is associated with multidrug efflux systems, especially the overexpression

of the adeABC genes, which encode an efflux pump [7, 8]. The AdeABC CB-839 purchase pump belongs to the resistance-nodulation-division (RND) family, which has a three-component structure [9]. Bacterial two-component systems (TCSs) play an important role in the regulation of adaptation to and signal transduction of environmental stimuli, including stress conditions [10]. TCSs are typically composed of a membrane-localized sensor with histidine kinase activity and a cytoplasmic response regulator (RR). Generally, upon AG-120 sensing environmental changes, signaling begins via autophosphorylation of Pexidartinib manufacturer the sensor protein at a conserved histidine residue. The phosphate is then transferred to an aspartic acid residue in the so-called receiver domain of the corresponding RR. Phosphorylation may induce conformational changes in RRs, which alters their DNA- binding properties, thus modulating downstream gene expression [11]. Importantly, the roles of Erlotinib manufacturer TCSs in the regulation of antimicrobial resistance have recently been documented in several species of bacteria [12–14]. Additionally, the AdeS-AdeR TCS controls genes encoding the AdeABC pump in A. baumannii[15]. AdeS is a sensor kinase, whereas AdeR is an RR.

Point mutations in AdeS and AdeR, or a truncation of AdeS due to an ISAba1 insertion, may be related to the overexpression of AdeABC, which leads to multidrug resistance [15, 16]. However, the existence of adeABC-overexpressing mutants without any mutations in adeRS[7] and the low expression of adeABC in a clinical strain of A. baumannii with the ISAbaI insertion in the adeRS operon [16] suggest that the regulation of adeABC gene expression is complicated, and other regulatory mechanisms may be involved. BaeSR is a TCS and is one of the five extracytoplasmic response pathways in Escherichia coli. BaeSR detects environmental signals and responds by altering the bacterial envelope [17]. The main function of the Bae response is to upregulate efflux pump expression in response to specific envelope-damaging agents [18]. Indole, flavonoids, and sodium tungstate have been shown to be novel inducers of the BaeSR response [18, 19].