Genetic basis of antibiotic resistance in pathogenic <i>Acinetobacter</i> species

Poirel, Laurent; Bonnin, Rémy A.; Nordmann, Patrice

doi:10.1002/iub.532

Cited by 142 publications

(116 citation statements)

References 47 publications

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“…For example, a retrospective study of ICU-acquired infections in the ICU of the National Cancer Institute of Mexico reported that A. baumannii was the causative agent of 6% of total hospital-acquired infections but disproportionately represented 60% of pneumonia and 25% of bloodstream infections (7). A. baumannii has rapidly evolved into a difficult-to-treat pathogen through acquisition, mostly via integrons and transposons, of multiple drug resistance genes that supplement the already high level of intrinsic drug resistance (8). A recent study analyzing more than 1,300 globally collected bloodstream isolates included over 150 A. baumannii isolates (4).…”

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confidence: 99%

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Williams

Neu

Gilbreath

et al. 2016

Appl Environ Microbiol

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Acinetobacter baumannii is an important emerging pathogen that is capable of causing many types of severe infection, especially in immunocompromised hosts. Since A. baumannii can rapidly acquire antibiotic resistance genes, many infections are on the verge of being untreatable, and novel therapies are desperately needed. To investigate the potential utility of copper-based antibacterial strategies against Acinetobacter infections, we characterized copper resistance in a panel of recent clinical A. baumannii isolates. Exposure to increasing concentrations of copper in liquid culture and on solid surfaces resulted in dose-dependent and strain-dependent effects; levels of copper resistance varied broadly across isolates, possibly resulting from identified genotypic variation among strains. Examination of the growth-phase-dependent effect of copper on A. baumannii revealed that resistance to copper increased dramatically in stationary phase. Moreover, A. baumannii biofilms were more resistant to copper than planktonic cells but were still susceptible to copper toxicity. Exposure of bacteria to subinhibitory concentrations of copper allowed them to better adapt to and grow in high concentrations of copper; this copper tolerance response is likely achieved via increased expression of copper resistance mechanisms. Indeed, genomic analysis revealed numerous putative copper resistance proteins that share amino acid homology to known proteins in Escherichia coli and Pseudomonas aeruginosa. Transcriptional analysis revealed significant upregulation of these putative copper resistance genes following brief copper exposure. Future characterization of copper resistance mechanisms may aid in the search for novel antibiotics against Acinetobacter and other highly antibiotic-resistant pathogens. IMPORTANCEAcinetobacter baumannii causes many types of severe nosocomial infections; unfortunately, some isolates have acquired resistance to almost every available antibiotic, and treatment options are incredibly limited. Copper is an essential nutrient but becomes toxic at high concentrations. The inherent antimicrobial properties of copper give it potential for use in novel therapeutics against drug-resistant pathogens. We show that A. baumannii clinical isolates are sensitive to copper in vitro, both in liquid and on solid metal surfaces. Since bacterial resistance to copper is mediated though mechanisms of efflux and detoxification, we identified genes encoding putative copper-related proteins in A. baumannii and showed that expression of some of these genes is regulated by the copper concentration. We propose that the antimicrobial effects of copper may be beneficial in the development of future therapeutics that target multidrug-resistant bacteria.

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confidence: 99%

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Williams

Neu

Gilbreath

et al. 2016

Appl Environ Microbiol

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“…An increased expression of the bla OXA-228-like genes was observed in a single isolate, mirroring the ␤-lactam resistance pattern observed and being mediated by promoter changes and not by strong promoters mediated by insertion sequences as shown for the bla OXA-51 gene in A. baumannii (5,22). That finding is different from those related to the overexpression of the intrinsic class D ␤-lactamase genes in A. baumannii, with insertion sequences ISAba1 and ISAba9 located upstream of the bla OXA-51 -like genes and providing strong promoters (5,17).…”

Section: Resultsmentioning

confidence: 75%

Biochemical and Genetic Characterization of Carbapenem-Hydrolyzing β-Lactamase OXA-229 from Acinetobacter bereziniae

Bonnin

Ocampo-Sosa

Poirel

et al. 2012

Antimicrob Agents Chemother

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Acinetobacter bereziniae (formerly Acinetobacter genomospecies 10) isolate Nec was recovered from a skin sample of a patient hospitalized in Paris, France. It was resistant to penicillins, penicillin-inhibitor combinations, and carbapenems. Cloning and expression in Escherichia coli identified the carbapenem-hydrolyzing class D ␤-lactamase OXA-229, which is weakly related to other oxacillinases (66% amino acid identity with the closest oxacillinase, OXA-58). It hydrolyzed penicillins, oxacillin, and imipenem but not expanded-spectrum cephalosporins. Sequencing of the genetic context of the bla OXA-229 gene did not identify an insertion sequence but did identify mutations in the promoter sequences in comparison to the fully susceptible A. bereziniae reference strain. The overexpression of bla OXA-229 in A. bereziniae Nec as a source of carbapenem resistance was identified by quantitative real-time PCR.A cinetobacter bereziniae, formely Acinetobacter genomospecies 10, was described as a new species of the genus Acinetobacter on the basis of DNA-DNA hybridization in 1986 by Bouvet et Grimont (1). A. bereziniae is a Gram-negative, strictly aerobic, oxidase-negative, and nonmotile coccobacillus (15). A. bereziniae was found to be responsible for health care-associated infections, including severe sepsis in an immunocompromised patient (12). Previous reports of ␤-lactamase-mediated resistance to carbapenems in A. bereziniae were related to the production of metallo-␤-lactamases, namely, IMP-1, SIM-1, and VIM-2 (14, 16).Some bacterial species naturally carry class D ␤-lactamase genes within their genome (22). In Acinetobacter species, intrinsically chromosomal genes encoding carbapenem-hydrolyzing class D ␤-lactamases (CHDLs) have been identified. Acinetobacter species A. baumannii naturally harbors bla OXA-51 -like genes, A. radioresistens harbors bla OXA-23 -like genes, and A. lwoffii bla and recently A. johnsonii, A. calcoaceticus, and A. haemolyticus have been shown to harbor bla OXA-211 -like, bla OXA-213 -like, and bla OXA-214 -like genes, respectively (4,6,9,19) (Fig. 1). Characterization of those naturally occurring CHDL-encoding genes provides additional tools for identification of Acinetobacter species.The present study was initiated by the isolation of two imipenem-nonsusceptible and non-baumannii Acinetobacter species. MATERIALS AND METHODSBacterial strains and plasmids. Identification of A. bereziniae isolates Nec and Baz was performed by using the API 32GN system (bioMérieux, Marcy l'Etoile, France) and was confirmed by 16S rRNA and partial rpoB gene sequencing, as described previously (7, 11). Reference strain Escherichia coli TOP10 was used as a host for clonings. A. bereziniae strain CIP70.12, isolated from a human wound in 1970, was used as the reference strain (15).MIC determinations. The antibiotic susceptibility profiles of the clinical and reference strains were determined by the agar dilution method, and the results were interpreted according to CLSI guidelines (2). MICs of cephalosporins and...

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“…ESBL genes are often associated with carbapenem and aminoglycoside resistance genes (10). In addition, integrons may contribute to beta-lactamase overproduction and dissemination (11); also, carrying integrons facilitate the spread of resistance genes among bacteria (12).…”

Section: Introductionmentioning

confidence: 99%

Emergence of Extensively Drug Resistant Acinetobacter baumannii-Encoding Integrons and Extended-Spectrum Beta-Lactamase Genes Isolated from Ventilator-Associated Pneumonia Patients

Rezai

Rafiei

Ahangarkani

et al. 2017

Jundishapur J Microbiol

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Background: Acinetobacter baumannii has increasingly become one of the most common pathogens causing ventilator-associated pneumonia (VAP). Objectives: In the present study, we aimed to assess the presence of extended-spectrum beta-lactamase (ESBL) and integron genes in A. baumannii isolates from VAP patients in the intensive care units (ICUs) of 18 hospitals in North of Iran. Methods: All patients, who were ventilated for at least 48 hours, were assessed daily for VAP. The minimum inhibitory concentrations were determined according to the standard protocol by the clinical and laboratory standards institute (CLSI). ESBL-producing A. baumannii was detected, using the double-disk synergy test. ESBL-positive A. baumannii isolates were screened for CTX, VEB, GES, SHV, int1, and int2 genes, using polymerase chain reaction (PCR) amplification. Results: In total, 29 out of 205 patients with nosocomial infections, admitted to ICUs during 2014 -2015, showed VAP caused by ESBL-producing A. baumannii. A total of 19 (65.51%) strains were extensively drug resistant (XDR). As the findings revealed, the rates of imipenem and colistin resistance were 55.2% and 34.5%, respectively. The prevalence of CTX, VEB, and SHV genes in ESBL-producing A. baumannii was 34.5%, 17.2%, and 96.6%, respectively. Also, 79.3% of the isolates had class 1 integrons, while 10.3% contained class 2 integrons. Conclusions: Presence of integrons in A. baumannii has been considerably associated with ESBL genes. The high rate of SHV and int1 genes highlights the necessity of avoiding aminoglycosides for empirical therapy. Although colistin was the most sensitive antibiotic in XDR strains in our region, due to the presence of patients with A. baumannii in ICUs, colistin resistance screening should be performed before empirical therapy for VAP, even for those without prior exposure to this antibiotic.

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Genetic basis of antibiotic resistance in pathogenic Acinetobacter species

Cited by 142 publications

References 47 publications

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

Biochemical and Genetic Characterization of Carbapenem-Hydrolyzing β-Lactamase OXA-229 from Acinetobacter bereziniae

Emergence of Extensively Drug Resistant Acinetobacter baumannii-Encoding Integrons and Extended-Spectrum Beta-Lactamase Genes Isolated from Ventilator-Associated Pneumonia Patients

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