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. 2021 Jun 17;65(7):e0051421.
doi: 10.1128/AAC.00514-21. Epub 2021 Jun 17.

Update on Multidrug Resistance Efflux Pumps in Acinetobacter spp

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Update on Multidrug Resistance Efflux Pumps in Acinetobacter spp

Vanessa Kornelsen et al. Antimicrob Agents Chemother. .

Abstract

Acinetobacter spp. have become of increased clinical importance as studies have shown the antimicrobial resistant potential of these species. Efflux pumps can lead to reduced susceptibility to a variety of antibiotics and are present in large number across Acinetobacter spp. There are six families of efflux pumps that have been shown to be of clinical relevance: the major facilitator superfamily (MFS), small multidrug resistance (SMR) family, ATP-binding cassette (ABC) family, multidrug and toxic compound extrusion (MATE) family, proteobacterial antimicrobial compound efflux (PACE) family, and the resistance-nodulation-division (RND) family. Much work has been done for understanding and characterizing the roles these efflux pumps play in relation to antimicrobial resistance and the physiology of these bacteria. RND efflux pumps, with their expansive substrate profiles, are a major component of Acinetobacter spp. antimicrobial resistance. New discoveries over the last decade have shed light on the complex regulation of these efflux pumps, leading to greater understanding and the potential of slowing the reduced susceptibility seen in these bacterial species.

Keywords: ABC transporters; Acinetobacter; AdeABC; AdeFGH; AdeIJK; MATE; PACE; RND; SMR; efflux pumps; multidrug resistance; regulation.

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Figures

FIG 1
FIG 1
Schematic of various efflux families and their location in the Gram-negative cell membrane. Efflux pumps that span the inner membrane are of the multidrug and toxic compound extrusion family (MATE), ATP-binding cassette family (ABC), proteobacterial antimicrobial compound efflux family (PACE), major facilitator superfamily (MFS), and small multidrug resistance family (SMR). Efflux pumps that span both the inner and outer membrane belong to the resistance-nodulation-division family (RND) and, as pictured, some ABC transporters are able to do so as well. Substrates are examples to indicate direction of transport.
FIG 2
FIG 2
The Transport Database 2.0 (102) was used to examine the proliferation of various efflux pump families in A. baumannii genomes (n = 16). The PACE family of transporters can currently not be found in the database and therefore has been excluded.
FIG 3
FIG 3
Regulation of AdeABC, AdeFGH, and AdeIJK efflux pumps in A. baumannii. Expression of the AdeABC pump (a) is activated by two two-component systems, AdeRS and BaeRS, low iron conditions, presence of human serum albumin, and presence of ppGpp. AdeFGH (b) expression is repressed by AdeL, a LysR-family protein, encoded upstream of the operon. Human serum albumin and DNA damage are known to increase adeFGH expression. AdeIJK (c) regulation involves the repression by TetR-type regulator AdeN and presence of human serum albumin, and activation by TCS BaeSR and ppGpp. Green solid arrows indicate direct activation of expression. Green dashed arrows indicate an unknown mechanism of activation of expression. Red solid lines indicate direct repression of expression. Red dashed lines indicate an unknown mechanism of inhibition of expression.

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