Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

ABSTRACTAcinetobacter baumanniiis an important emerging pathogen that is capable of causing many types of severe infection, especially in immunocompromised hosts. SinceA. baumanniican 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 againstAcinetobacterinfections, we characterized copper resistance in a panel of recent clinicalA. baumanniiisolates. 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 onA. baumanniirevealed that resistance to copper increased dramatically in stationary phase. Moreover,A. baumanniibiofilms 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 inEscherichia coliandPseudomonas 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 againstAcinetobacterand other highly antibiotic-resistant pathogens.IMPORTANCEAcinetobacter baumanniicauses 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 thatA. baumanniiclinical isolates are sensitive to copperin 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 inA. baumanniiand 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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Variants of Tn 6924 , a Novel Tn 7 Family Transposon Carrying the bla NDM Metallo-β-Lactamase and 14 Copies of the aphA6 Amikacin Resistance Genes Found in Acinetobacter baumannii

Microbiology Spectrum ◽

10.1128/spectrum.01745-21 ◽

2022 ◽

Author(s):

Riti Mann ◽

Rayane Rafei ◽

Cindy Gunawan ◽

Christopher J. Harmer ◽

Mohammad Hamidian

Keyword(s):

Acinetobacter Baumannii ◽

Resistance Genes ◽

Resistance Mechanisms ◽

Sequence Type ◽

Content Type ◽

Carbapenem Resistant ◽

Globally Distributed

To date, efforts to study the resistance mechanisms of carbapenem-resistant Acinetobacter baumannii have been largely focused on the two major globally distributed clones (GC1 and GC2). ST85 is an emerging sequence type, and unlike other clones, it is associated with the carriage of the bla NDM gene.

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Environmental Spread of New Delhi Metallo-β-Lactamase-1-Producing Multidrug-Resistant Bacteria in Dhaka, Bangladesh

Applied and Environmental Microbiology ◽

10.1128/aem.00793-17 ◽

2017 ◽

Vol 83 (15) ◽

Cited By ~ 32

Author(s):

Mohammad Aminul Islam ◽

Moydul Islam ◽

Rashedul Hasan ◽

M. Iqbal Hossain ◽

Ashikun Nabi ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Tap Water ◽

Antibiotic Resistance Genes ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

New Delhi ◽

Multidrug Resistant Bacteria ◽

Content Type ◽

Wastewater Samples

ABSTRACT Resistance to carbapenem antibiotics through the production of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the bla NDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P < 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among bla NDM-1-positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including bla CTX-M-1 (80%), bla CTX-M-15 (63%), bla TEM (76%), bla SHV (33%), bla CMY-2 (16%), bla OXA-48-like (2%), bla OXA-1 (53%), and bla OXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying bla NDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community. IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the bla NDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospital-adjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.

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Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

Journal of Medical Microbiology ◽

10.1099/jmm.0.001347 ◽

2021 ◽

Vol 70 (4) ◽

Author(s):

Balaram Khamari ◽

Prakash Kumar ◽

Bulagonda Eswarappa Pradeep

Keyword(s):

Antimicrobial Agents ◽

Efflux Pump ◽

Treatment Options ◽

Strong Association ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistant Bacteria ◽

Drug Resistant ◽

Content Type ◽

Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

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Merging Metagenomics and Spatial Epidemiology To Understand the Distribution of Antimicrobial Resistance Genes from Enterobacteriaceae in Wild Owls

Applied and Environmental Microbiology ◽

10.1128/aem.00571-20 ◽

2020 ◽

Vol 86 (20) ◽

Author(s):

Elizabeth A. Miller ◽

Julia B. Ponder ◽

Michelle Willette ◽

Timothy J. Johnson ◽

Kimberly L. VanderWaal

Keyword(s):

Antimicrobial Resistance ◽

Resistance Genes ◽

Spatial Epidemiology ◽

Anthropogenic Sources ◽

Resistant Bacteria ◽

Metagenomic Sequencing ◽

Wild Animals ◽

Natural Ecosystems ◽

Content Type ◽

Antimicrobial Resistance Genes

ABSTRACT Antimicrobial resistance (AMR) is a well-documented phenomenon in bacteria from many natural ecosystems, including wild animals. However, the specific determinants and spatial distribution of resistant bacteria and antimicrobial resistance genes (ARGs) in the environment remain incompletely understood. In particular, information regarding the importance of anthropogenic sources of AMR relative to that of other biological and ecological influences is lacking. We conducted a cross-sectional study of AMR in great horned owls (Bubo virginianus) and barred owls (Strix varia) admitted to a rehabilitation center in the midwestern United States. A combination of selective culture enrichment and shotgun metagenomic sequencing was used to identify ARGs from Enterobacteriaceae. Overall, the prevalence of AMR was comparable to that in past studies of resistant Enterobacteriaceae in raptors, with acquired ARGs being identified in 23% of samples. Multimodel regression analyses identified seasonality and owl age to be important predictors of the likelihood of the presence of ARGs, with birds sampled during warmer months being more likely to harbor ARGs than those sampled during cooler months and with birds in their hatch year being more likely to harbor β-lactam ARGs than adults. Beyond host-specific determinants, ARG-positive owls were also more likely to be recovered from areas of high agricultural land cover. Spatial clustering analyses identified a significant high-risk cluster of tetracycline resistance gene-positive owls in the southern sampling range, but this could not be explained by any predictor variables. Taken together, these results highlight the complex distribution of AMR in natural environments and suggest that both biological and anthropogenic factors play important roles in determining the emergence and persistence of AMR in wildlife. IMPORTANCE Antimicrobial resistance (AMR) is a multifaceted problem that poses a worldwide threat to human and animal health. Recent reports suggest that wildlife may play an important role in the emergence, dissemination, and persistence of AMR. As such, there have been calls for better integration of wildlife into current research on AMR, including the use of wild animals as biosentinels of AMR contamination in the environment. A One Health approach can be used to gain a better understanding of all AMR sources and pathways, particularly those at the human-animal-environment interface. Our study focuses on this interface in order to assess the effect of human-impacted landscapes on AMR in a wild animal. This work highlights the value of wildlife rehabilitation centers for environmental AMR surveillance and demonstrates how metagenomic sequencing within a spatial epidemiology framework can be used to address questions surrounding AMR complexity in natural ecosystems.

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Accumulation of Antibiotic Resistance Genes in Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Lineage 2, Global Clone 1, from Outbreaks in 2012–2013 at a Tehran Burns Hospital

mSphere ◽

10.1128/msphere.00164-20 ◽

2020 ◽

Vol 5 (2) ◽

Cited By ~ 2

Author(s):

Masoumeh Douraghi ◽

Johanna J. Kenyon ◽

Parisa Aris ◽

Mahla Asadian ◽

Sedighe Ghourchian ◽

...

Keyword(s):

Middle East ◽

Acinetobacter Baumannii ◽

Resistance Genes ◽

Carbapenem Resistance ◽

Antibiotic Resistant ◽

Content Type ◽

Carbapenem Resistant ◽

East Region ◽

Lineage 2 ◽

Middle East Region

ABSTRACT The worldwide distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) has become a global concern, particularly in countries where antibiotic prescription is not tightly regulated. However, knowledge of the genomic aspects of CRAB from many parts of the world is still limited. Here, 50 carbapenem-resistant A. baumannii isolates recovered at a single hospital in Tehran, Iran, during several outbreaks in 2012 and 2013 were found to be resistant to multiple antibiotics. They were examined using PCR mapping and multilocus sequence typing (MLST). All Iranian strains belonged to sequence type 328 in the Institut Pasteur MLST scheme (ST328IP), a single-locus variant of ST81IP, and all Iranian strains contained two carbapenem resistance genes, oxa23 and oxa24. The oxa23 gene is in the transposon Tn2006 in AbaR4, which interrupts the chromosomal comM gene. Phylogenetic analysis using whole-genome sequence (WGS) data for 9 isolates showed that they belonged to the same clade, designated the ST81/ST328 clade, within lineage 2 of global clone 1 (GC1). However, there were two groups that included either KL13 or KL18 at the K locus (KL) for capsular polysaccharide synthesis and either a tet39 or an aadB resistance gene, respectively. The genetic context of the resistance genes was determined, and the oxa24 (OXA-72 variant) and tet39 (tetracycline resistance) genes were each in a pdif module in different plasmids. The aadB gene cassette (which encodes gentamicin, kanamycin, and tobramycin resistance) was harbored by pRAY*, and the aphA6 gene (which encodes amikacin resistance) and sul2 gene (which encodes sulfamethoxazole resistance) were each harbored by a different plasmid. The sequences obtained here will underpin future studies of GC1 CRAB strains from the Middle East region. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii strains are among the most critical antibiotic-resistant bacteria causing hospital-acquired infections and treatment failures. The global spread of two clones has been responsible for the bulk of the resistance, in particular, carbapenem resistance. However, there is a substantial gap in our knowledge of which clones and which specific lineages within each clone are circulating in many parts of the world, including Africa and the Middle East region. This is the first genomic analysis of carbapenem-resistant A. baumannii strains from Iran. All the isolates, from a single hospital, belonged to lineage 2 of global clone 1 (GC1) but fell into two groups distinguished by genes in the locus for capsule biosynthesis. The analysis suggests a potential origin of multiply antibiotic-resistant lineage 2 in the Middle East region and highlights the ongoing evolution of carbapenem-resistant GC1 A. baumannii strains. It will enhance future studies on the local and global GC1 population structure.

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ESKAPE Bacteria and Extended-Spectrum-β-Lactamase-Producing Escherichia coli Isolated from Wastewater and Process Water from German Poultry Slaughterhouses

Applied and Environmental Microbiology ◽

10.1128/aem.02748-19 ◽

2020 ◽

Vol 86 (8) ◽

Cited By ~ 7

Author(s):

Mykhailo Savin ◽

Gabriele Bierbaum ◽

Jens Andre Hammerl ◽

Céline Heinemann ◽

Marijo Parcina ◽

...

Keyword(s):

Escherichia Coli ◽

Wastewater Treatment ◽

Resistance Genes ◽

Wastewater Treatment Plants ◽

Process Water ◽

Resistant Bacteria ◽

Content Type ◽

E Coli ◽

Extended Spectrum ◽

Clinically Relevant Bacteria

ABSTRACT The wastewater of livestock slaughterhouses is considered a source of antimicrobial-resistant bacteria with clinical relevance and may thus be important for their dissemination into the environment. To get an overview of their occurrence and characteristics, we investigated process water (n = 50) from delivery and unclean areas as well as wastewater (n = 32) from the in-house wastewater treatment plants (WWTPs) of two German poultry slaughterhouses (slaughterhouses S1 and S2). The samples were screened for ESKAPE bacteria (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) and Escherichia coli. Their antimicrobial resistance phenotypes and the presence of extended-spectrum-β-lactamase (ESBL), carbapenemase, and mobilizable colistin resistance genes were determined. Selected ESKAPE bacteria were epidemiologically classified using different molecular typing techniques. At least one of the target species was detected in 87.5% (n = 28/32) of the wastewater samples and 86.0% (n = 43/50) of the process water samples. The vast majority of the recovered isolates (94.9%, n = 448/472) was represented by E. coli (39.4%), the A. calcoaceticus-A. baumannii (ACB) complex (32.4%), S. aureus (12.3%), and K. pneumoniae (10.8%), which were widely distributed in the delivery and unclean areas of the individual slaughterhouses, including their wastewater effluents. Enterobacter spp., Enterococcus spp., and P. aeruginosa were less abundant and made up 5.1% of the isolates. Phenotypic and genotypic analyses revealed that the recovered isolates exhibited diverse resistance phenotypes and β-lactamase genes. In conclusion, wastewater effluents from the investigated poultry slaughterhouses exhibited clinically relevant bacteria (E. coli, methicillin-resistant S. aureus, K. pneumoniae, and species of the ACB and Enterobacter cloacae complexes) that contribute to the dissemination of clinically relevant resistances (i.e., blaCTX-M or blaSHV and mcr-1) in the environment. IMPORTANCE Bacteria from livestock may be opportunistic pathogens and carriers of clinically relevant resistance genes, as many antimicrobials are used in both veterinary and human medicine. They may be released into the environment from wastewater treatment plants (WWTPs), which are influenced by wastewater from slaughterhouses, thereby endangering public health. Moreover, process water that accumulates during the slaughtering of poultry is an important reservoir for livestock-associated multidrug-resistant bacteria and may serve as a vector of transmission to occupationally exposed slaughterhouse employees. Mitigation solutions aimed at the reduction of the bacterial discharge into the production water circuit as well as interventions against their further transmission and dissemination need to be elaborated. Furthermore, the efficacy of in-house WWTPs needs to be questioned. Reliable data on the occurrence and diversity of clinically relevant bacteria within the slaughtering production chain and in the WWTP effluents in Germany will help to assess their impact on public and environmental health.

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Occurrence of cop-like copper resistance genes among bacteria isolated from a water distribution system

Canadian Journal of Microbiology ◽

10.1139/m95-087 ◽

1995 ◽

Vol 41 (7) ◽

pp. 642-646 ◽

Cited By ~ 22

Author(s):

Chuzhao Lin ◽

Betty H. Olson

Keyword(s):

Pseudomonas Syringae ◽

Resistance Genes ◽

Distribution System ◽

Water Distribution ◽

Water Distribution System ◽

Culture Media ◽

Copper Resistance ◽

Copper Tolerance ◽

Resistant Bacteria ◽

Copper Resistance Genes

The occurrence of cop-like copper resistance determinants homologous to the cop genes of Pseudomonas syringae among bacteria isolated from a water distribution system experiencing copper corrosion was investigated in this study. It was found that at least 49% of the copper-resistant bacteria and less than 15% of the copper-sensitive isolates possessed a cop homolog. The occurrence of this determinant in the copper-resistant population correlated with the degree of copper tolerance exhibited by the bacteria. The effect of organic substances present in the culture media on the empirical degree of bacterial copper tolerance is also discussed.Key words: copper resistance genes, water distribution system, cop.

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Co-selection of antibiotic and heavy metal resistance in freshwater bacteria

Journal of Limnology ◽

10.4081/jlimnol.2016.1198 ◽

2016 ◽

Vol 75 (s2) ◽

Cited By ~ 34

Author(s):

Andrea Di Cesare ◽

Ester Eckert ◽

Gianluca Corno

Keyword(s):

Heavy Metal ◽

Resistance Genes ◽

Heavy Metal Resistance ◽

Resistance Mechanisms ◽

Metal Resistance ◽

Resistant Bacteria ◽

Human Pathogens ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

Selection Of

Antibiotic resistant bacteria are found in most environments, especially in highly anthropized waters. A direct correlation between human activities (e.g., pollution) and spread and persistence of antibiotic resistant bacteria (ARB) and resistance genes (ARGs) within the resident bacterial communities appears more and more obvious. Furthermore, the threat posed for human health by the presence of ARB and ARGs in these environments is enhanced by the risk of horizontal gene transfer of resistance genes to human pathogens. Although the knowledge on the spread of antibiotic resistances in waters is increasing, the understanding of the driving factors determining the selection for antibiotic resistance in the environment is still scarce. Antibiotic pollution is generally coupled with contamination by heavy metals (HMs) and other chemicals, which can also promote the development of resistance mechanisms, often through co-selecting for multiple resistances. The co-selection of heavy metal resistance genes and ARGs in waters, sediments, and soils, increases the complexity of the ecological role of ARGs, and reduces the effectiveness of control actions. In this mini-review we present the state-of-the-art of the research on antibiotic- and HM-resistance and their connection in the environment, with a focus on HM pollution and aquatic environments. We review the spread and the persistence of HMs and/or ARB, and how it influences their respective gene co-selection. In the last chapter, we propose Lake Orta, a system characterized by an intensive HM pollution followed by a successful restoration of the chemistry of the water column, as a study-site to evaluate the spread and selection of HMs and antibiotic resistances in heavily disturbed environments.

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Copper Resistance Mechanisms of Biomining Bacteria and Archaea Living under Extremely High Concentrations of Metals

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.71-73.279 ◽

2009 ◽

Vol 71-73 ◽

pp. 279-282 ◽

Cited By ~ 1

Author(s):

A. Orell ◽

C.A. Navarro ◽

Carlos A. Jerez

Keyword(s):

Resistance Mechanisms ◽

Metal Resistance ◽

Copper Resistance ◽

Inorganic Polyphosphate ◽

Resistance Determinants ◽

High Metal ◽

Pi Complex ◽

Cu Resistance ◽

High Concentrations ◽

Cu Tolerance

Extremophiles such as the acidophilic Sulfolobus metallicus (Archaea) and Acidithiobacillus ferrooxidans (Bacteria) can resist Cu (CuSO4) concentrations of 200 mM and 800 mM respectively. These microorganisms are important in biomining processes to extract copper and other metals. A. ferrooxidans grown at low Cu concentrations (5 mM) expressed genes coding for ATPases most likely involved in pumping the metal from the cytoplasm to the periplasm of the bacterium. At 100 mM Cu the previous systems were repressed and there was a great induction in the expression of efflux systems known to use the proton motive force energy to export the metal outside the cell. These Cu-resistance determinants from A. ferrooxidans were found to be functional since when expressed in Escherichia coli they conferred higher Cu tolerance to it. Novel Cu-resistance determinants for A. ferrooxidans were found and characterized. S. metallicus possessed at least 2 CopM metallochaperones and 2 CopA ATPases whose expressions were induced by Cu (5 to 50 mM). Furthermore, we previously reported that both microorganisms accumulate high levels of inorganic polyphosphate (PolyP) and that intracellular Cu concentration stimulates polyP hydrolysis. The resulting Pi would then be transported out of the cell as a metal-Pi complex to detoxify the cells. In addition, our results suggest that at high Cu concentrations polyP could also provide energy for the metal efflux. All the data suggest that both biomining microorganisms use different systems to respond to Cu depending on the extracellular concentrations of the metal and suggest that the presence of different additional systems to respond to Cu may explain the extremely high metal resistance of these extremophiles.

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Horizontal Transfer of the OXA-24 Carbapenemase Gene via Outer Membrane Vesicles: a New Mechanism of Dissemination of Carbapenem Resistance Genes in Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00929-10 ◽

2011 ◽

Vol 55 (7) ◽

pp. 3084-3090 ◽

Cited By ~ 134

Author(s):

Carlos Rumbo ◽

Esteban Fernández-Moreira ◽

María Merino ◽

Margarita Poza ◽

Jose Antonio Mendez ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Outer Membrane ◽

Resistance Genes ◽

Carbapenem Resistance ◽

Membrane Vesicles ◽

Outer Membrane Vesicles ◽

Content Type ◽

Class D ◽

Carbapenemase Gene

ABSTRACTThe resistance ofAcinetobacter baumanniistrains to carbapenems is a worrying problem in hospital settings. The main mechanism of carbapenem resistance is the expression of β-lactamases (metalloenzymes or class D enzymes). The mechanisms of the dissemination of these genes amongA. baumanniistrains are not fully understood. In this study we used two carbapenem-resistant clinical strains ofA. baumannii(AbH12O-A2 and AbH12O-CU3) expressing the plasmid-borneblaOXA-24gene (plasmids pMMA2 and pMMCU3, respectively) to demonstrate thatA. baumanniireleases outer membrane vesicles (OMVs) duringin vitrogrowth. The use of hybridization studies enabled us to show that these OMVs harbored theblaOXA-24gene. The incubation of these OMVs with the carbapenem-susceptibleA. baumanniiATCC 17978 host strain yielded full resistance to carbapenems. The presence of the original plasmids harboring theblaOXA-24gene was detected in strain ATCC 17978 after the transformation of OMVs. New OMVs harboringblaOXA-24were released byA. baumanniiATCC 17978 after it was transformed with the original OMV-mediated plasmids, indicating the universality of the process. We present the first experimental evidence that clinical isolates ofA. baumanniimay release OMVs as a mechanism of horizontal gene transfer whereby carbapenem resistance genes are delivered to surroundingA. baumanniibacterial isolates.

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