Resistance-Nodulation-Cell Division-Type Efflux Pump Involved in Aminoglycoside Resistance in Acinetobacter baumannii Strain BM4454

Abstract

Multidrug-resistant strain Acinetobacter baumannii BM4454 was isolated from a patient with a urinary tract infection. The adeB gene, which encodes a resistance-nodulation-cell division (RND) protein, was detected in this strain by PCR with two degenerate oligodeoxynucleotides. Insertional inactivation of adeB in BM4454, which generated BM4454-1, showed that the corresponding protein was responsible for aminoglycoside resistance and was involved in the level of susceptibility to other drugs including fluoroquinolones, tetracyclines, chloramphenicol, erythromycin, trimethoprim, and ethidium bromide. Study of ethidium bromide accumulation in BM4454 and BM4454-1, in the presence or in the absence of carbonyl cyanide m-chlorophenylhydrazone, demonstrated that AdeB was responsible for the decrease in intracellular ethidium bromide levels in a proton motive force-dependent manner. The adeB gene was part of a cluster that included adeA and adeC which encodes proteins homologous to membrane fusion and outer membrane proteins of RND-type three-component efflux systems, respectively. The products of two upstream open reading frames encoding a putative twocomponent regulatory system might be involved in the regulation of expression of the adeABC gene cluster.

Molecular characterization of carbapenem-resistant Acinetobacter species in an Irish university hospital: predominance of Acinetobacter genomic species 3

“…Other mechanisms of resistance may also have contributed to aminoglycoside resistance in our isolates. In particular, overexpression of multidrug efflux pumps such as AdeABC confers resistance to aminoglycosides and several other classes of antimicrobial agents in A. baumannii (Magnet et al, 2001). …”

Prevalence of eight resistance-nodulation-division efflux pump genes in epidemiologically characterized Acinetobacter baumannii of worldwide origin

“…In Gram-negative bacteria, various mechanisms are associated with a multidrug resistance (MDR) phenotype, including enzymic drug inactivation/modification, target alteration, low membrane permeability and active efflux. Of these, increased expression of chromosomally encoded efflux pumps has been proposed as the first step in the development of a MDR phenotype (Piddock, 2006) and several reports have been published showing decreased susceptibility to multiple antibiotics due to the overexpression of normally cryptic efflux systems in A. baumannii (Coyne et al, 2010;Damier-Piolle et al, 2008;Higgins et al, 2010a;Magnet et al, 2001).…”

“…The proton gradient across the membrane serves as a driving force. To date, three RND efflux systems have been described in A. baumannii: AdeABC (Magnet et al, 2001), AdeFGH (Coyne et al, 2010) and AdeIJK (Damier-Piolle et al, 2008).…”

Structure and Function of the PiuA and PirA Siderophore-Drug Receptors from Pseudomonas aeruginosa and Acinetobacter baumannii

“…Besides its chromosomally encoded AmpC-type beta lactamase (20), A. baumannii frequently harbors class B and D carbapenemases (21) and extended-spectrum beta-lactamases (ESBL) of the PER, GES, and VEB types (22). RNDtype efflux systems, including AdeABC (23), AdeIJK (24), and AdeFGH (25), further contribute to the multidrug resistance phenotype of clinical isolates. A. baumannii harbors between 21 and 27 TonB-dependent receptors compared to 35 in P. aeruginosa (26).…”