Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

Abstract

Abstract:Acinetobacter baumannii is an opportunistic pathogen which play the more and more greater role in the pathogenicity of the human. It is often attached with the hospital environment, in which is able easily to survive for many days even in adverse conditions. Acinetobacter baumannii is the species responsible for a serious nosocomial infections, especially in the intensive care units. Option of surviving in natural niches, and in the hospital environment could also be associated with the efflux pump mechanisms. Mechanisms of efflux universally appear in all cells (eukaryotic and prokaryotic) and play the physiological important role. In prokaryote, the main functions are evasion of such naturally produced molecules, removal of metabolic products and toxins. These pumps could also be involved in an early stage of infection, such as adhesion to host cells and the colonization. Importantly, they remove commonly used antibiotics from the cell in therapy of infections caused by these bacteria. Efflux pumps exemplify a unique phenomenon in drug resistance: a single mechanism causing resistance against several different classes of antibiotics. In Acinetobacter baumannii, the AdeABC efflux pump, a member of the resistance-nodulation-cell division family (RND), has been well characterized. Aminoglicosides, tetracyclines, erythromycin, chloramphenicol, trimethoprim, fluoroquinolones, some β-lactams, and also recently tigecycline, were found to be substrates for this pump. Drugs, as substrates for the AdeABC pump, can increase the expression of the AdeABC genes, leading to multidrug resistance (MDR). From this reason, treatment failure and death caused by Acinetobacter baumannii infections or underlying diseases are common. Because the AdeABC pump is widespread in Acinetobacter baumannii, similarly to other pumps in Gram-negative and Gram-positive bacteria, exists a need of searching a new therapeutic solutions. Specific efflux inhibitors of pumps (EPIs), including AdeABC inhibitors, could be suppress the activity of pumps and restore the sensitivity of such important bacteria as Acinetobacter baumannii to commonly used antibiotic.

Acinetobacter baumannii: biology and drug resistance — role of carbapenemases

“…In A. baumannii the major efflux pump associated with carbapenem resistance is AdeABC. This EP belongs to RND family and is comprised of three-components: AdeA -membrane fusion protein, AdeB -inner membrane protein channel, and AdeC -outer membrane protein channel [61]. Overexpression of this EP is regulated by adeS and adeR genes contributing to increased resistance to antimicrobials, inter alia: meropenem, fluoroquinolones, tetracyclines, chloramphenicol as well as aminoglycosides [10].…”

In vitro activity of various combinations of antimicrobials against carbapenem-resistant Acinetobacter species in Singapore

“…Drugs, as substrates for the AdeABC pump, can increase the expression of AdeABC genes, leading to multidrug resistance. 30 Although AdeABC multidrug efflux pumps are intrinsic to A. baumannii, and the AdeDE and AdeXY pumps are found predominantly in Acinetobacter genomospecies 3, 31 we did not have any additional data to confirm the overexpression of these efflux genes, which can contribute to multidrug resistance in our isolates. Hence, with the knowledge of different carbapenemase genes (which confer expression of different types of carbapenemases) in our isolates, we can only prostulate why carbapenem as a part of combination antibiotics does not work in synergism, whereas combinations using non-b-lactams work better against our isolates.…”

Bombas de expulsión multidrogas en Acinetobacter baumannii y resistencia a antimicrobianos

“…De acuerdo a Sánchez y cols 16 , la mayoría de las bombas de expulsión multidrogas de bacilos gramnegativos pertenece a la familia RND. Estas bombas están formadas por tres componentes: una proteína transportadora ubicada en la membrana interna, una proteína accesoria periplasmática o proteína de fusión de membrana y una proteína de membrana externa o porina [29][30][31] . Los genes que codifican a los distintos componentes de estas bombas de expulsión se encuentran en el cromosoma bacteriano, generalmente en forma de operones 32 .…”