scholarly journals Distribution of Intrinsic Plasmid Replicase Genes and Their Association with Carbapenem-Hydrolyzing Class D β-Lactamase Genes in European Clinical Isolates of Acinetobacter baumannii

2011 ◽  
Vol 55 (5) ◽  
pp. 2154-2159 ◽  
Author(s):  
Kevin J. Towner ◽  
Benjamin Evans ◽  
Laura Villa ◽  
Katrina Levi ◽  
Ahmed Hamouda ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Horizontal Transmission ◽  
Antibiotic Resistance Genes ◽  
General System ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Content Type ◽  
Class D ◽  
Genes Encoding ◽  
Plasmid Mobilization

ABSTRACTNinety-six genetically diverse multidrug-resistant clinical isolates ofAcinetobacter baumanniifrom 25 hospitals in 17 European countries were screened by PCR for specific carbapenemase-hydrolyzing class D β-lactamase (CHDL) genes and by PCR-based replicon typing for the presence of 19 different plasmid replicase (rep) gene homology groups (GRs). Results were confirmed by DNA sequencing where necessary. All 96 isolates contained at least 1 (with a maximum of 4) of the 19 groups ofrepgenes. Groups detected were GR6 (repAci6; 93 isolates), GR2 (includingrepAci1 [67 isolates] andrepAci2 [3 isolates]), GR16 (repApAB49; 12 isolates), GR12 (p2ABSDF0001; 10 isolates), GR3 (repAci3; 4 isolates), GR4 (repAci4; 3 isolates), GR10 (repAciX; 1 isolate), and GR14 (repp4AYE; 1 isolate). Variations inrepgene content were observed even among epidemiologically related isolates. Genes encoding OXA-58-like CHDLs (22 isolates) were associated with carriage of therepAci1,repAci3,repAci4, andrepAciX genes, genes encoding OXA-40-like CHDLs (6 isolates) were associated withrepAci2 and p2ABSDF0001, and genes encoding OXA-23-like CHDLs (8 isolates) were associated withrepAci1. Most intrinsicAcinetobacterplasmids are non-self-transferable, but the almost ubiquitousrepAci6 gene was strongly associated with a potentialtralocus that could serve as a general system for plasmid mobilization and consequent horizontal transmission of plasmids and their associated antibiotic resistance genes among strains ofA. baumannii.

scholarly journals Novel Phage Lysin Capable of Killing the Multidrug-Resistant Gram-Negative Bacterium Acinetobacter baumannii in a Mouse Bacteremia Model

2015 ◽  
Vol 59 (4) ◽  
pp. 1983-1991 ◽  
Author(s):  
Rolf Lood ◽  
Benjamin Y. Winer ◽  
Adam J. Pelzek ◽  
Roberto Diez-Martinez ◽  
Mya Thandar ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genomic Library ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Genes Encoding

ABSTRACTAcinetobacter baumannii, a Gram-negative multidrug-resistant (MDR) bacterium, is now recognized as one of the more common nosocomial pathogens. Because most clinical isolates are found to be multidrug resistant, alternative therapies need to be developed to control this pathogen. We constructed a bacteriophage genomic library based on prophages induced from 13A. baumanniistrains and screened it for genes encoding bacteriolytic activity. Using this approach, we identified 21 distinct lysins with different activities and sequence diversity that were capable of killingA. baumannii. The lysin (PlyF307) displaying the greatest activity was further characterized and was shown to efficiently kill (>5-log-unit decrease) all testedA. baumanniiclinical isolates. Treatment with PlyF307 was able to significantly reduce planktonic and biofilmA. baumanniibothin vitroandin vivo. Finally, PlyF307 rescued mice from lethalA. baumanniibacteremia and as such represents the first highly active therapeutic lysin specific for Gram-negative organisms in an array of native lysins found inAcinetobacterphage.

scholarly journals In Vitro Activity of Sulbactam-Durlobactam against Acinetobacter baumannii-calcoaceticus Complex Isolates Collected Globally in 2016 and 2017

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Sarah M. McLeod ◽  
Samir H. Moussa ◽  
Meredith A. Hackel ◽  
Alita A. Miller
Keyword(s):  
Acinetobacter Baumannii ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Single Amino Acid ◽  
Content Type ◽  
Level Of Activity ◽  
Severe Infections ◽  
Sources Of Infection

ABSTRACT Acinetobacter baumannii-calcoaceticus complex (ABC) organisms cause severe infections that are difficult to treat due to preexisting antibiotic resistance. Sulbactam-durlobactam (formerly sulbactam-ETX2514) (SUL-DUR) is a β-lactam–β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by ABC organisms, including multidrug-resistant (MDR) strains. The in vitro antibacterial activities of SUL-DUR and comparator agents were determined by broth microdilution against 1,722 clinical isolates of ABC organisms collected in 2016 and 2017 from 31 countries across Asia/South Pacific, Europe, Latin America, the Middle East, and North America. Over 50% of these isolates were resistant to carbapenems. Against this collection of global isolates, SUL-DUR had a MIC50/MIC90 of 1/2 μg/ml compared to a MIC50/MIC90 of 8/64 μg/ml for sulbactam alone. This level of activity was found to be consistent across organisms, regions, sources of infection, and subsets of resistance phenotypes, including MDR and extensively drug-resistant isolates. The SUL-DUR activity was superior to those of the tested comparators, with only colistin having similar potency. Whole-genome sequencing of the 39 isolates (2.3%) with a SUL-DUR MIC of >4 μg/ml revealed that these strains encoded either the metallo-β-lactamase NDM-1, which durlobactam does not inhibit, or single amino acid substitutions near the active site of penicillin binding protein 3 (PBP3), the primary target of sulbactam. In summary, SUL-DUR demonstrated potent antibacterial activity against recent, geographically diverse clinical isolates of ABC organisms, including MDR isolates.

scholarly journals Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D β-Lactamase of Acinetobacter baumannii

2015 ◽  
Vol 60 (1) ◽  
pp. 75-86 ◽  
Author(s):  
Shivendra Pratap ◽  
Madhusudhanarao Katiki ◽  
Preet Gill ◽  
Pravindra Kumar ◽  
Dasantila Golemi-Kotra
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii ◽  
Active Site ◽  
Active Sites ◽  
Multidrug Resistant ◽  
Crystal Structure Analysis ◽  
Content Type ◽  
Class D ◽  
Enzyme Species ◽  
Hydroxyethyl Group

ABSTRACTCarbapenem-hydrolyzing class D β-lactamases (CHDLs) are a subgroup of class D β-lactamases, which are enzymes that hydrolyze β-lactams. They have attracted interest due to the emergence of multidrug-resistantAcinetobacter baumannii, which is not responsive to treatment with carbapenems, the usual antibiotics of choice for this bacterium. Unlike other class D β-lactamases, these enzymes efficiently hydrolyze carbapenem antibiotics. To explore the structural requirements for the catalysis of carbapenems by these enzymes, we determined the crystal structure of the OXA-58 CHDL ofA. baumanniifollowing acylation of its active-site serine by a 6α-hydroxymethyl penicillin derivative that is a structural mimetic for a carbapenem. In addition, several point mutation variants of the active site of OXA-58, as identified by the crystal structure analysis, were characterized kinetically. These combined studies confirm the mechanistic relevance of a hydrophobic bridge formed over the active site. This structural feature is suggested to stabilize the hydrolysis-productive acyl-enzyme species formed from the carbapenem substrates of this enzyme. Furthermore, our structural studies provide strong evidence that the hydroxyethyl group of carbapenems samples different orientations in the active sites of CHDLs, and the optimum orientation for catalysis depends on the topology of the active site allowing proper closure of the active site. We propose that CHDLs use the plasticity of the active site to drive the mechanism of carbapenem hydrolysis toward efficiency.

scholarly journals Pseudomonas aeruginosa Clinical Isolates in Nepal Coproducing Metallo-β-Lactamases and 16S rRNA Methyltransferases

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Tatsuya Tada ◽  
Kayo Shimada ◽  
Kazuhito Satou ◽  
Takashi Hirano ◽  
Bharat M. Pokhrel ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
16S Rrna ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Content Type ◽  
First Report ◽  
Genes Encoding

ABSTRACT A total of 11 multidrug-resistant Pseudomonas aeruginosa clinical isolates were obtained in Nepal. Four of these isolates harbored genes encoding one or more carbapenemases (DIM-1, NDM-1, and/or VIM-2), and five harbored genes encoding a 16S rRNA methyltransferase (RmtB4 or RmtF2). A novel RmtF variant, RmtF2, had a substitution (K65E) compared with the same gene in RmtF. To our knowledge, this is the first report describing carbapenemase- and 16S rRNA methyltransferase-coproducing P. aeruginosa clinical isolates in Nepal.

scholarly journals Draft Genome Sequences of Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii

2017 ◽  
Vol 5 (5) ◽  
Author(s):  
Keesha E. Erickson ◽  
Nancy E. Madinger ◽  
Anushree Chatterjee
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Genome Sequences ◽  
Content Type ◽  
University Of Colorado ◽  
The University

ABSTRACT We report here the draft genome sequences of two clinically isolated Acinetobacter baumannii strains. These samples were obtained from patients at the University of Colorado Hospital in 2007 and 2013 and encode an estimated 20 and 13 resistance genes, respectively.

scholarly journals Pathogenicity Genomic Island-Associated CrpP-Like Fluoroquinolone-Modifying Enzymes among Pseudomonas aeruginosa Clinical Isolates in Europe

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
José Manuel Ortiz de la Rosa ◽  
Patrice Nordmann ◽  
Laurent Poirel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Genomic Island ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Genomic Islands ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Genes Encoding

ABSTRACT Many transferable quinolone resistance mechanisms have been identified in Gram-negative bacteria. The plasmid-encoded 65-amino-acid-long ciprofloxacin-modifying enzyme CrpP was recently identified in Pseudomonas aeruginosa isolates. We analyzed a collection of 100 clonally unrelated and multidrug-resistant P. aeruginosa clinical isolates, among which 46 were positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. These crpP-like genes were chromosomally located as part of pathogenicity genomic islands.

scholarly journals Activity of the β-Lactamase Inhibitor LN-1-255 against Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Juan Carlos Vázquez-Ucha ◽  
María Maneiro ◽  
Marta Martínez-Guitián ◽  
John Buynak ◽  
Christopher R. Bethel ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Kinetics Parameters ◽  
Clinical Issue ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Continued Use ◽  
Global Threat ◽  
Lactamase Inhibitor

ABSTRACT The number of infections caused by Gram-negative pathogens carrying carbapenemases is increasing, and the group of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is especially problematic. Several clinically important CHDLs have been identified in Acinetobacter baumannii, including OXA-23, OXA-24/40, OXA-58, OXA-143, OXA-235, and the chromosomally encoded OXA-51. The selection and dissemination of carbapenem-resistant A. baumannii strains constitutes a serious global threat. Carbapenems have been successfully utilized as last-resort antibiotics for the treatment of multidrug-resistant A. baumannii infections. However, the spread of OXA carbapenemases is compromising the continued use of these antimicrobials. In response to this clinical issue, it is necessary and urgent to design and develop new specific inhibitors with efficacy against these enzymes. The aim of this work was to characterize the inhibitory activity of LN-1-255 (a 6-alkylidene-2-substituted penicillin sulfone) and compare it to that of two established inhibitors (avibactam and tazobactam) against the most relevant enzymes of each group of class D carbapenemases in A. baumannii. The β-lactamase inhibitor LN-1-255 demonstrated excellent microbiological synergy and inhibition kinetics parameters against all tested CHDLs and a significantly higher activity than tazobactam and avibactam. A combination of carbapenems and LN-1-255 was effective against A. baumannii class D carbapenemases. Docking assays confirmed the affinity of LN-1-255 for the active site of these enzymes. LN-1-255 represents a potential new β-lactamase inhibitor that may have a significant role in eradicating infections caused by A. baumannii isolates carrying CHDLs.

scholarly journals Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

2016 ◽  
Vol 60 (3) ◽  
pp. 1801-1818 ◽  
Author(s):  
Nabil Karah ◽  
Chinmay Kumar Dwibedi ◽  
Karin Sjöström ◽  
Petra Edquist ◽  
Anders Johansson ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Point Mutations ◽  
Antibiotic Resistance Genes ◽  
Opportunistic Pathogen ◽  
Clinical Isolates ◽  
Aminoglycoside Resistance ◽  
Content Type ◽  
Carbapenem Resistant

Acinetobacter baumanniihas emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates ofA. baumanniicollected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n= 16) and CC25 (n= 7). Resistance to carbapenems was related toblaOXA-23(20 isolates),blaOXA-24/40-like(6 isolates),blaOXA-467(1 isolate), and ISAba1-blaOXA-69(1 isolate). Ceftazidime resistance was associated withblaPER-7in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylasearmAgene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, ΔTn6279, Ab-ST3-aadB, and different assemblies of Tn6020and TnaphA6. Importantly, a number of circular forms related to the IS26or ISAba125composite transposons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes.

scholarly journals Globally Expanding Carbapenemase Finally Appears in Spain: Nosocomial Outbreak of Acinetobacter baumannii Producing Plasmid-Encoded OXA-23 in Barcelona, Spain

2013 ◽  
Vol 57 (10) ◽  
pp. 5155-5157 ◽  
Author(s):  
Noraida Mosqueda ◽  
Paula Espinal ◽  
Clara Cosgaya ◽  
Sergio Viota ◽  
Virginia Plasensia ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Clinical Isolates ◽  
Nosocomial Outbreak ◽  
Content Type ◽  
Hospital Outbreak

ABSTRACTResistance ofAcinetobacter baumanniiclinical isolates to carbapenems is on the rise worldwide mainly in association with the production of OXA-23. Until recently, however, OXA-23 was absent in Spain. In this work, we report the molecular characterization of a hospital outbreak of OXA-23-producingA. baumanniiin Barcelona caused by a multidrug-resistant (MDR) clone belonging to international clone IC-II/sequence type ST85 between October 2010 and May 2011.blaOXA-23was carried in a plasmid of 90 kb and located within the composite transposon Tn2006.

scholarly journals Genomic Analysis of the Multidrug-Resistant Acinetobacter baumannii Strain MDR-ZJ06 Widely Spread in China

2011 ◽  
Vol 55 (10) ◽  
pp. 4506-4512 ◽  
Author(s):  
Hua Zhou ◽  
Tongwu Zhang ◽  
Dongliang Yu ◽  
Borui Pi ◽  
Qing Yang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Resistance Island

ABSTRACTWe previously reported that the multidrug-resistant (MDR)Acinetobacter baumanniistrain MDR-ZJ06, belonging to European clone II, was widely spread in China. In this study, we report the whole-genome sequence of this clinically important strain. A 38.6-kb AbaR-type genomic resistance island (AbaR22) was identified in MDR-ZJ06. AbaR22 has a structure similar to those of the resistance islands found inA. baumanniistrains AYE and AB0057, but it contained only a few antibiotic resistance genes. The region of resistant gene accumulation as previously described was not found in AbaR22. In the chromosome of the strain MDR-ZJ06, we identified the geneblaoxa-23in a composite transposon (Tn2009). Tn2009shared the backbone with otherA. baumanniitransponsons that harborblaoxa-23, but it was bracketed by two ISAba1elements which were transcribed in the same orientation. MDR-ZJ06 also expressed thearmAgene on its plasmid pZJ06, and this gene has the same genetic environment as thearmAgene of theEnterobacteriaceae. These results suggest variability of resistance acquisition even in closely relatedA. baumanniistrains.

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