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

Nowak, Jennifer; Seifert, Harald; Higgins, Paul G.

doi:10.1099/jmm.0.000069

Cited by 29 publications

(25 citation statements)

References 28 publications

(37 reference statements)

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“…Of these resistance mechanisms, A. baumannii encodes for a large number of drug efflux pumps with broad substrate profiles that contribute toward the high level of intrinsic resistance to structurally-unrelated agents (Fournier et al, 2000 ; Ling et al, 2016 ). These resistance determinants facilitate the evolution of acquired resistance (Lin et al, 2009 , 2017b ; Coyne et al, 2011 ; Nowak et al, 2015 ; Ling et al, 2016 ). Indeed, the drug efflux pumps that are known to mediate intrinsic and/or acquired resistance to conventional antibiotics and biocides include the efflux systems of the resistance-nodulation-cell division (RND) superfamily (AdeABC, AdeFGH, AdeIJK, and AbeD) (Rumbo et al, 2013 ; Srinivasan et al, 2015 ; Ling et al, 2016 ), AmvA pump of the major facilitator superfamily (MFS) (Rajamohan et al, 2010a ), AbeM of the multidrug and toxic compound extrusion (MATE) family (Su et al, 2005 ), QacE and QacEΔ1 of the small drug resistance (SMR) family (Fournier et al, 2000 ; Taitt et al, 2014 ; Babaei et al, 2015 ), and AceI of the proteobacterial antimicrobial compound efflux (PACE) family (Hassan et al, 2013 , 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Reduced Susceptibility to Biocides in Clinical Isolates of Acinetobacter baumannii

et al. 2017

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Active efflux is regarded as a common mechanism for antibiotic and biocide resistance. However, the role of many drug efflux pumps in biocide resistance in Acinetobacter baumannii remains unknown. Using biocide-resistant A. baumannii clinical isolates, we investigated the incidence of 11 known/putative antimicrobial resistance efflux pump genes (adeB, adeG, adeJ, adeT1, adeT2, amvA, abeD, abeM, qacE, qacEΔ1, and aceI) and triclosan target gene fabI through PCR and DNA sequencing. Reverse transcriptase quantitative PCR was conducted to assess the correlation between the efflux pump gene expression and the reduced susceptibility to triclosan or chlorhexidine. The A. baumannii isolates displayed high levels of reduced susceptibility to triclosan, chlorhexidine, benzalkonium, hydrogen peroxide, and ethanol. Most tested isolates were resistant to multiple antibiotics. Efflux resistance genes were widely distributed and generally expressed in A. baumannii. Although no clear relation was established between efflux pump gene expression and antibiotic resistance or reduced biocide susceptibility, triclosan non-susceptible isolates displayed relatively increased expression of adeB and adeJ whereas chlorhexidine non-susceptible isolates had increased abeM and fabI gene expression. Increased expression of adeJ and abeM was also demonstrated in multiple antibiotic resistant isolates. Exposure of isolates to subinhibitory concentrations of triclosan or chlorhexidine induced gene expression of adeB, adeG, adeJ and fabI, and adeB, respectively. A point mutation in FabI, Gly95Ser, was observed in only one triclosan-resistant isolate. Multiple sequence types with the major clone complex, CC92, were identified in high level triclosan-resistant isolates. Overall, this study showed the high prevalence of antibiotic and biocide resistance as well as the complexity of intertwined resistance mechanisms in clinical isolates of A. baumannii, which highlights the importance of antimicrobial stewardship and resistance surveillance in clinics.

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Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Reduced Susceptibility to Biocides in Clinical Isolates of Acinetobacter baumannii

et al. 2017

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“…These tripartite efflux structures were first identified and characterized in E. coli and P. aeruginosa strains [25,26]. Advances in biochemistry and molecular biology enabled the discovery of numerous related RND pumps in nearly all clinically important bacteria [27][28][29][30].…”

Section: Efflux Pumps-based Mdr In Gram-negative Bacteriamentioning

confidence: 99%

Multidrug efflux pumps and their role in antibiotic and antiseptic resistance: a pharmacodynamic perspective

Alibert

Diarra

Hernandez

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed. Expert opinion: Efflux pumps are new targets for the development of adjuvant in antibiotic treatments by of efflux pump inhibition. They may allow us to rejuvenate old antibiotics acting on their concen-tration inside the bacteria and thus potentiating their activity while blocking the release of virulence factors. It is a pharmacodynamic challenge to finalize new combined therapy. KEYWORDSEfflux pump; Gram-negative bacteria; antibiotic; multidrug resistance; inhibitor Article highlights• Efflux pumps play a major role in multidrug resistance in Gram-negative bacteria • The pharmacodynamic role of RND efflux pumps in antibiotic resis-tance opens up new perspectives to alternative therapeutics • Targeting efflux pumps consists in solving the problems of polyse-lectivity, drug accumulation, membrane permeability and pathogeni-city related to bacterial resistance mechanisms • How to validate efflux pumps as target for new combined therapy?• Efflux pump inhibitor could be used as adjuvant in antibiotic treatments

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“…Some studies have used molecular typing to elucidate the epidemic features of Tgc-R A. baumannii . With molecular-based detection, some researchers have investigated the prevalence of certain resistance-determinant genes, such as Nowark’s work that studied the prevalence of resistance nodulation division (RND)-type efflux pumps among 144 epidemiological A. baumannii isolates from locations around the world 7 .…”

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“…In addition, global regulators involved in the SOS responsive system, adaption or virulence-related co-evolution may also contribute to increased Tgc resistance. Cyclic-di-GMP is a secondary messenger involved in bacterial adhesive ability and extracellular polysaccharide (EPS) biogenesis, and it may facilitate resistance through biofilm barrier formation or through altered metabolism within the biofilm 7 10 11 . Other related AR genes include those that encode metabolic enzymes, such as methyltransferase, acyltransferase and hydrogenase 12 , and some of their functions have been studied in wet lab experiments.…”

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confidence: 99%

Analysis of tigecycline resistance development in clinical Acinetobacter baumannii isolates through a combined genomic and transcriptomic approach

Liu

Cui

Zheng

et al. 2016

Sci Rep

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Tigecycline (Tgc) is considered a last-resort antibiotic for the treatment of multi-drug resistant bacteria. To study Tgc resistance development in the important nosocomial pathogen Acinetobacter baumannii, we adopted six clinical isolates from three patients undergoing antibiotic treatment, and bacterial genomic sequences and seven strand-specific transcriptomes were studied. Interestingly, the Tgc-intermediate 2015ZJAB1 only differed from Tgc-resistant 2015ZJAB2 in an SNP-clustered region including OprD, a sugar-type MFS permease, and a LuxR-type transcriptional regulator. Surprisingly, an almost identical region was found in 2015ZJAB3, which supports the possibility of a homologous recombination event that increased Tgc resistance. Furthermore, comparative transcriptomic analysis identified significantly regulated genes associated with Tgc resistance, which was verified using qRT-PCR. Three enriched COG categories included amino acid transport and metabolism, transcription, and inorganic ion transport and metabolism. KEGG analysis revealed common features under Tgc conditions, including up regulated benzoate degradation and a less active TCA cycle. This may be related to selective antimicrobial pressure in the environment and adaptation by lowering metabolism. This study provides the first report of an in vivo evolutionary process that included a putative homologous recombination event conferring Tgc resistance in clinical A. baumannii isolates in which transcriptome analysis revealed resistance-conferring genes and related metabolism characteristics.

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

Cited by 29 publications

References 28 publications

Molecular Characterization of Reduced Susceptibility to Biocides in Clinical Isolates of Acinetobacter baumannii

Molecular Characterization of Reduced Susceptibility to Biocides in Clinical Isolates of Acinetobacter baumannii

Multidrug efflux pumps and their role in antibiotic and antiseptic resistance: a pharmacodynamic perspective

Analysis of tigecycline resistance development in clinical Acinetobacter baumannii isolates through a combined genomic and transcriptomic approach

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