Functional Characterization of AbeD, an RND-Type Membrane Transporter in Antimicrobial Resistance in Acinetobacter baumannii

Srinivasan, Vijaya Bharathi; Venkataramaiah, Manjunath; Mondal, Amitabha; Rajamohan, Govindan

doi:10.1371/journal.pone.0141314

Cited by 24 publications

(33 citation statements)

References 36 publications

(59 reference statements)

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“…Identification of AoSoxR Target Genes-To identify SoxRregulated genes, we used the A. oleivorans genome and transcriptome data indicating possible SoxR binding sites (24,(31)(32)(33). Although five possible candidate promoters (AOLE_ 16635 encoding a putative L-PSP endoribonucleases, AOLE_ 18450 encoding a membrane protein, argT, scpA, and hisZ) were found using a putative SoxR binding site, two of them (scpA and hisZ) were not induced by RACs.…”

Section: Resultsmentioning

confidence: 99%

“…Among them, AOLE_16640 (co-transcribed with sinE) and AOLE_05515 were directly regulated by activated SoxR. It was recently reported that the abuO gene encoding a TolC-like outer membrane protein and the abeD gene encoding a RNDtype membrane transporter of A. baumannii AYE were directly regulated by SoxR (31,32). A putative outer membrane protein (AOLE_18125) that showed 94% amino acid identity with AbuO was up-regulated 4.1-fold with PMS treatment; however, there was no difference in the presence of PQ in our transcriptome analyses.…”

Section: Discussionmentioning

confidence: 99%

“…␤-Galactosidase activity by EH46 harboring pCR2.1-TOPO (empty vector) is not shown in Fig. 1 because there was no difference between the untreated and treated conditions (range of Miller units: [27][28][29][30][31][32][33][34][35].…”

Section: Methodsmentioning

confidence: 99%

“…ADP1 (31)(32)(33). The Acinetobacter SoxR-binding consensus sequence was constructed as 5Ј-TTGACYTCAASTKAASTTKARSTTKS-3Ј (where Y indicates C or T; S indicates G or C; K indicates G or T; and R indicates G or A).…”

Section: Methodsmentioning

confidence: 99%

“…Severe growth defects in the Acinetobacter oxyR mutant grown in hexadecane-amended conditions indicated that OxyR is important for the elimination of ROS during hexadecane biodegradation (30). It was recently reported that SoxR from Acinetobacter baumannii AYE can bind the promoter regions of two genes, abuO and abeD, which encode a TolC-like outer membrane protein and an RND-type membrane transporter, respectively (31,32). Our bioinformatics study suggested that Acinetobacter species, including A. oleivorans DR1, possess a SoxR binding site in the promoter regions of several genes, including a gene coding an L-PSP endoribonuclease, which is one of the five known categories of gene products controlled by SoxR in non-enteric bacteria (33).…”

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confidence: 99%

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Lineage-specific SoxR-mediated Regulation of an Endoribonuclease Protects Non-enteric Bacteria from Redox-active Compounds

Kim

Park

Imlay

et al. 2017

Journal of Biological Chemistry

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Edited by F. Peter GuengerichBacteria use redox-sensitive transcription factors to coordinate responses to redox stress. The [2Fe-2S] cluster-containing transcription factor SoxR is particularly tuned to protect cells against redox-active compounds (RACs). In enteric bacteria, SoxR is paired with a second transcription factor, SoxS, that activates downstream effectors. However, SoxS is absent in nonenteric bacteria, raising questions as to how SoxR functions. Here, we first show that SoxR of Acinetobacter oleivorans displayed similar activation profiles in response to RACs as did its homolog from Escherichia coli but controlled a different set of target genes, including sinE, which encodes an endoribonuclease. Expression, gel mobility shift, and mutational analyses indicated that sinE is a direct target of SoxR. Redox potentials and permeability of RACs determined optimal sinE induction. Bioinformatics suggested that only a few ␥-and ␤-proteobacteria might have SoxR-regulated sinE. Purified SinE, in the presence of Mg 2؉ ions, degrades rRNAs, thus inhibiting protein synthesis. Similarly, pretreatment of cells with RACs demonstrated a role for SinE in promoting persistence in the presence of antibiotics that inhibit protein synthesis. Our data improve our understanding of the physiology of soil microorganisms by suggesting that both non-enteric SoxR and its target SinE play protective roles in the presence of RACs and antibiotics.Oxidative stress is an unavoidable consequence of aerobic and anaerobic metabolism when cells are exposed to O 2 . Bacteria have evolved to harbor defense mechanisms against various reactive oxygen species (ROS).4 Bacteria protect themselves by activating ROS-sensing transcription factors, including OxyR and PerR, that detect hydrogen peroxide (H 2 O 2 ) using cysteine residues and iron, respectively, and SoxR, which responds to superoxide or redox-active compounds (RACs) using a [2Fe-2S] cluster (1-3). Bacteria can produce many natural RACs, such as pyocyanin (PYO), actinorhodin, and plumbagin (PL), that act as antibiotics, toxic compounds, and quorum signals (4). RACs can generate toxic doses of ROS inside cells by mediating electron transfer from redox enzymes to O 2 . When Escherichia coli is exposed to RACs, SoxR is activated by the oxidation of its [2Fe-2S] cluster, and it subsequently induces the transcription of soxS (5-8). SoxS then induces the transcription of numerous genes involved in the repair of oxidatively damaged enzymes and DNA and the elimination of ROS (9 -12). However, the E. coli-SoxRS paradigm does not apply to nonenteric bacteria because of the absence of SoxS and no induction of many known E. coli SoxRS regulon (13-18). Surprisingly, activated SoxR can directly induce several genes (lpxC, aroF, sodA, and mgtA) in E. coli by binding their promoters without soxS (16). SoxR can be activated directly by RACs rather than by superoxide, as evidenced by the fact that RACs can oxidize the [2Fe-2S] 1ϩ cluster of SoxR even under anaerobic conditions (1, 2, 12). Activated S...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%