Diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with tigecycline resistance in Acinetobacter baumannii

Gerson, Stefanie; Nowak, Jennifer; Zander, Esther; Ertel, Julia; Wen, Yurong; Krut, Oleg; Seifert, Harald; Higgins, Paul G.

doi:10.1093/jac/dky083

Cited by 64 publications

(89 citation statements)

References 41 publications

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“…The AdeABC efflux pump was confirmed to export not only tigecycline but also beta-lactam, fluoroquinolone, aminoglycoside and chloramphenicol (Coyne et al, 2011;Xu et al, 2019). As mentioned in previous studies, the overexpression of AdeABC efflux pump has been shown to be related to amino acid substitutions in AdeRS TCS (Gerson et al, 2018;Yoon et al, 2013). Our results indicated that the two amino acid substitutions in AdeRS TCS may be associated to the overexpression of AdeABC efflux pump.…”

Section: Discussionsupporting

confidence: 80%

AdeABC Efflux Pump Controlled by AdeRS Two Component System Conferring Resistance to Tigecycline, Omadacycline and Eravacycline in Clinical Carbapenem Resistant Acinetobacter nosocomialis

et al. 2020

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Section: Discussionsupporting

confidence: 80%

AdeABC Efflux Pump Controlled by AdeRS Two Component System Conferring Resistance to Tigecycline, Omadacycline and Eravacycline in Clinical Carbapenem Resistant Acinetobacter nosocomialis

et al. 2020

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“…Increased expression can result from mutations in the AdeRS two-component system. In A. nosocomialis M2, the AdeR and AdeS proteins did not contain amino acid substitutions previously associated with increased AdeABC expression (Marchand et al, 2004 ; Yoon et al, 2013 ; Gerson et al, 2018 ). Based on this information, we propose that the AdeABC genes are tightly regulated by AdeRS and the levels of expression in the M2 strain do not contribute to intrinsic resistance.…”

Section: Discussionmentioning

confidence: 70%

Acinetobacter nosocomialis: Defining the Role of Efflux Pumps in Resistance to Antimicrobial Therapy, Surface Motility, and Biofilm Formation

2018

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Acinetobacter nosocomialis is a member of the Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) complex. Increasingly, reports are emerging of the pathogenic profile and multidrug resistance (MDR) phenotype of this species. To define novel therapies to overcome resistance, we queried the role of the major efflux pumps in A. nosocomialis strain M2 on antimicrobial susceptibility profiles. A. nosocomialis strains with the following mutations were engineered by allelic replacement; ΔadeB, ΔadeJ, and ΔadeB/adeJ. In these isogenic strains, we show that the ΔadeJ mutation increased susceptibility to beta-lactams, beta-lactam/beta-lactamase inhibitors, chloramphenicol, monobactam, tigecycline, and trimethoprim. The ΔadeB mutation had a minor effect on resistance to certain beta-lactams, rifampicin and tigecycline. In addition, the ΔadeJ mutation resulted in a significant decrease in surface motility and a minor decrease in biofilm formation. Our results indicate that the efflux pump, AdeIJK, has additional roles outside of antibiotic resistance in A. nosocomialis.

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“…Tigecycline is an interesting therapeutic option to treat infection by carbapenem-resistant Gram-negative bacteria [ 59 ]. However, the isolates evaluated herein demonstrated resistance to this antimicrobial by the Etest ® and microdilution methods.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and clonal dynamics of nosocomial blaOXA-23 producing XDR Acinetobacter baumannii

et al. 2018

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The emergence of infections associated to new antimicrobial resistance in Acinetobacter baumannii (Ab) genotypes represents a major challenge. In this context, this study aimed to determine the diversity of resistance mechanisms and investigate clonal dissemination and predominant sequence types (STs) in multidrug-resistant Ab strains of clinical (tracheal aspirate, n = 17) and environmental (surface, n = 6) origins. Additionally, the major clones found in clinical (A) and environmental (H) strains had their complete genomes sequenced. All strains were submitted to polymerase chain reactions (PCR) for the detection of the ISAba1/blaOXA-51-like and ISAba1/blaOXA-23-like genes, while the expression of genes encoding the carO porin, AdeABC (adeB), AdeFGH (adeG), and AdeIJK (adeJ) efflux pumps was determined by real time PCR (qPCR). Most of the strains were characterized as extensively drug-resistant (XDR) with high minimal inhibitory concentrations (MICs) detected for tigecycline and carbapenems. Associations between ISAba1/OXA-51 and ISAba1/OXA-23 were observed in 91.3% and 52.2% of the strains, respectively. Only the adeB gene was considered hyper-expressed. Furthermore, most of the strains analyzed by the MuLtilocus Sequence-Typing (MLST) were found to belong to the clonal complex 113 (CC113). In addition, a new ST, ST1399, belonging to CC229, was also discovered herein. Strains analyzed by whole genome sequencing presented resistance genes linked to multidrug-resistance phenotypes and confirmed the presence of Tn2008, which provides high levels carbapenem-resistance.

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Diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with tigecycline resistance in Acinetobacter baumannii

Abstract: This study provides an insight into the different mechanisms associated with tigecycline resistance using a genomic approach and points out the importance of considering adeRS and adeN as markers for tigecycline-resistant A. baumannii isolates.

Cited by 64 publications

References 41 publications

AdeABC Efflux Pump Controlled by AdeRS Two Component System Conferring Resistance to Tigecycline, Omadacycline and Eravacycline in Clinical Carbapenem Resistant Acinetobacter nosocomialis

AdeABC Efflux Pump Controlled by AdeRS Two Component System Conferring Resistance to Tigecycline, Omadacycline and Eravacycline in Clinical Carbapenem Resistant Acinetobacter nosocomialis

Acinetobacter nosocomialis: Defining the Role of Efflux Pumps in Resistance to Antimicrobial Therapy, Surface Motility, and Biofilm Formation

Molecular characterization and clonal dynamics of nosocomial blaOXA-23 producing XDR Acinetobacter baumannii

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