scholarly journals Analysis of blaCHDL Genes and Insertion Sequences Related to Carbapenem Resistance in Acinetobacter baumannii Clinical Strains Isolated in Warsaw, Poland

2021 ◽  
Vol 22 (5) ◽  
pp. 2486
Author(s):  
Alicja Słoczyńska ◽  
Matthew E. Wand ◽  
Stefan Tyski ◽  
Agnieszka E. Laudy
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
Drug Susceptibility ◽  
Resistance Mechanisms ◽  
Whole Genome Sequence ◽  
Insertion Sequences ◽  
Mlst Scheme ◽  
Treatment And Prevention ◽  
Class D ◽  
Insertion Elements

Acinetobacter baumannii is an important cause of nosocomial infections worldwide. The elucidation of the carbapenem resistance mechanisms of hospital strains is necessary for the effective treatment and prevention of resistance gene transmission. The main mechanism of carbapenem resistance in A. baumannii is carbapenemases, whose expressions are affected by the presence of insertion sequences (ISs) upstream of blaCHDL genes. In this study, 61 imipenem-nonsusceptible A. baumannii isolates were characterized using phenotypic (drug-susceptibility profile using CarbaAcineto NP) and molecular methods. Pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) methods were utilized for the genotyping. The majority of isolates (59/61) carried one of the following acquired blaCHDL genes: blaOXA-24-like (39/59), ISAba1-blaOXA-23-like (14/59) or ISAba3-blaOXA-58-like (6/59). Whole genome sequence analysis of 15 selected isolates identified the following intrinsic blaOXA-66 (OXA-51-like; n = 15) and acquired class D β-lactamases (CHDLs): ISAba1-blaOXA-23 (OXA-23-like; n = 7), ISAba3-blaOXA-58-ISAba3 (OXA-58-like; n = 2) and blaOXA-72 (OXA-24-like; n = 6). The isolates were classified into 21 pulsotypes using PFGE, and the representative 15 isolates were found to belong to sequence type ST2 of the Pasteur MLST scheme from the global IC2 clone. The Oxford MLST scheme revealed the diversity among these studied isolates, and identified five sequence types (ST195, ST208, ST208/ST1806, ST348 and ST425). CHDL-type carbapenemases and insertion elements upstream of the blaCHDL genes were found to be widespread among Polish A. baumannii clinical isolates, and this contributed to their carbapenem resistance.

scholarly journals OXA-58, a Novel Class D β-Lactamase Involved in Resistance to Carbapenems in Acinetobacter baumannii

2005 ◽  
Vol 49 (1) ◽  
pp. 202-208 ◽  
Author(s):  
Laurent Poirel ◽  
Sophie Marqué ◽  
Claire Héritier ◽  
Christine Segonds ◽  
Gérard Chabanon ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Reference Strain ◽  
Carbapenem Resistance ◽  
Amino Acid Identity ◽  
Cloning And Expression ◽  
Acid Identity ◽  
Carbapenem Resistant ◽  
Class D ◽  
Insertion Elements

ABSTRACT A carbapenem-resistant Acinetobacter baumannii strain was isolated in Toulouse, France, in 2003. Cloning and expression in Escherichia coli identified the carbapenem-hydrolyzing β-lactamase OXA-58, which is weakly related (less than 50% amino acid identity) to other oxacillinases. It hydrolyzed penicillins, oxacillin, and imipenem but not expanded-spectrum cephalosporins. The bla OXA-58 gene was located on a ca. 30-kb non-self-transferable plasmid. After electrotransformation in the A. baumannii CIP7010T reference strain, it conferred reduced susceptibility to carbapenems. The bla OXA-58 gene was bracketed by two novel ISAba3-like insertion elements. This study describes a newly characterized β-lactamase that may contribute to carbapenem resistance in A. baumannii.

scholarly journals OXA-235, a Novel Class D β-Lactamase Involved in Resistance to Carbapenems in Acinetobacter baumannii

2013 ◽  
Vol 57 (5) ◽  
pp. 2121-2126 ◽  
Author(s):  
Paul G. Higgins ◽  
Francisco J. Pérez-Llarena ◽  
Esther Zander ◽  
Ana Fernández ◽  
Germán Bou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
The United States ◽  
Amino Acid Sequences ◽  
Insertion Sequences ◽  
Content Type ◽  
Resistance Determinants ◽  
Class D ◽  
Amino Acid Variants

ABSTRACTWe investigated the mechanism of carbapenem resistance in 10Acinetobacter baumanniistrains isolated from the United States and Mexico between 2005 and 2009. The detection of known metallo-β-lactamase or carbapenem-hydrolyzing oxacillinase (OXA) genes by PCR was negative. The presence of plasmid-encoded carbapenem resistance genes was investigated by transformation ofA. baumanniiATCC 17978. Shotgun cloning experiments and sequencing were performed, followed by the expression of a novel β-lactamase inA. baumannii. Three novel OXA enzymes were identified, OXA-235 in 8 isolates and the amino acid variants OXA-236 (Glu173-Val) and OXA-237 (Asp208-Gly) in 1 isolate each. The deduced amino acid sequences shared 85% identity with OXA-134, 54% to 57% identities with the acquired OXA-23, OXA-24, OXA-58, and OXA-143, and 56% identity with the intrinsic OXA-51 and, thus, represent a novel subclass of OXA. The expression of OXA-235 inA. baumanniiled to reduced carbapenem susceptibility, while cephalosporin MICs were unaffected. Genetic analysis revealed thatblaOXA-235,blaOXA-236, andblaOXA-237were bracketed between two ISAba1insertion sequences. In addition, the presence of these acquired β-lactamase genes might result from a transposition-mediated mechanism. This highlights the propensity ofA. baumanniito acquire multiple carbapenem resistance determinants.

scholarly journals Characterization of the First OXA-10 Natural Variant with Increased Carbapenemase Activity

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Stathis D. Kotsakis ◽  
Carl-Fredrik Flach ◽  
Mohammad Razavi ◽  
D. G. Joakim Larsson
Keyword(s):  
Carbapenem Resistance ◽  
Catalytic Efficiency ◽  
Resistance Mechanisms ◽  
Broad Host Range ◽  
Evolutionary Potential ◽  
Class D ◽  
Steady State Kinetic ◽  
Natural Variant ◽  
Hydrolyzing Enzymes ◽  
Catalytic Motif

ABSTRACTWhile carbapenem resistance in Gram-negative bacteria is mainly due to the production of efficient carbapenemases, β-lactamases with a narrower spectrum may also contribute to resistance when combined with additional mechanisms. OXA-10-type class D β-lactamases, previously shown to be weak carbapenemases, could represent such a case. In this study, two novel OXA-10 variants were identified as the sole carbapenem-hydrolyzing enzymes in meropenem-resistant enterobacteria isolated from hospital wastewater and found by next-generation sequencing to express additional β-lactam resistance mechanisms. The new variants, OXA-655 and OXA-656, were carried by two related IncQ1 broad-host-range plasmids. Compared to the sequence of OXA-10, they both harbored a Thr26Met substitution, with OXA-655 also bearing a leucine instead of a valine in position 117 of the SAV catalytic motif. Susceptibility profiling of laboratory strains replicating the naturalblaOXAplasmids and of recombinant clones expressing OXA-10 and the novel variants in an isogenic background indicated that OXA-655 is a more efficient carbapenemase. The carbapenemase activity of OXA-655 is due to the Val117Leu substitution, as shown by steady-state kinetic experiments, where thekcatof meropenem hydrolysis was increased 4-fold. In contrast, OXA-655 had no activity toward oxyimino-β-lactams, while its catalytic efficiency against oxacillin was significantly reduced. Moreover, the Val117Leu variant was more efficient against temocillin and cefoxitin. Molecular dynamics indicated that Val117Leu affects the position 117-Leu155 interaction, leading to structural shifts in the active site that may alter carbapenem alignment. The evolutionary potential of OXA-10 enzymes toward carbapenem hydrolysis combined with their spread by promiscuous plasmids indicates that they may pose a future clinical threat.

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

2011 ◽  
Vol 55 (7) ◽  
pp. 3084-3090 ◽  
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.

scholarly journals Diversity of Oxacillinases and Sequence Types in Carbapenem-Resistant Acinetobacter baumannii from Austria

2021 ◽  
Vol 18 (4) ◽  
pp. 2171 ◽  
Author(s):  
Andrea Grisold ◽  
Josefa Luxner ◽  
Branka Bedenić ◽  
Magda Diab-Elschahawi ◽  
Michael Berktold ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genetic Background ◽  
Regional Differences ◽  
Carbapenem Resistance ◽  
Carbapenem Resistant ◽  
Class D ◽  
Acinetobacter Spp ◽  
First Time ◽  
Sequence Types ◽  
Significant Health

Carbapenem-resistant Acinetobacter baumannii is a significant health problem worldwide. A multicenter study on A. baumannii was performed to investigate the molecular epidemiology and genetic background of carbapenem resistance of A. baumannii isolates collected from 2014–2017 in Austria. In total, 117 non-repetitive Acinetobacter spp. assigned to A. baumannii (n = 114) and A. pittii (n = 3) were collected from four centers in Austria. The isolates were uniformly resistant to piperacillin/tazobactam, ceftazidime, and carbapenems, and resistance to imipenem and meropenem was 97.4% and 98.2%, respectively. The most prominent OXA-types were OXA-58-like (46.5%) and OXA-23-like (41.2%), followed by OXA-24-like (10.5%), with notable regional differences. Carbapenem-hydrolyzing class D carbapenemases (CHDLs) were the only carbapenemases found in A.baumannii isolates in Austria since no metallo-β-lactamases (MBLs) nor KPC or GES carbapenemases were detected in any of the isolates. One-third of the isolates harbored multiple CHDLs. The population structure of A. baumannii isolates from Austria was found to be very diverse, while a total of twenty-three different sequence types (STs) were identified. The most frequent was ST195 found in 15.8%, followed by ST218 and ST231 equally found in 11.4% of isolates. Two new ST types, ST2025 and ST2026, were detected. In one A. pittii isolate, blaOXA-143-like was detected for the first time in Austria.

scholarly journals Whole-genome sequence analysis reveals evolution of antimicrobial resistance in a Ugandan colistin resistant Acinetobacter baumannii

2020 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Mobile Genetic Element ◽  
Whole Genome Sequence ◽  
Broad Host Range ◽  
Insertion Sequences ◽  
Drug Resistant ◽  
Genetic Element ◽  
Resistance Evolution

AbstractIn recent times, pan-drug resistant Acinetobacter baumannii have emerged and continue to spread among critically ill patients, this poses an urgent risk to global and local human health. This study sought to provide the first genomic analysis of a pan-drug resistant Acinetobacter baumannii from Uganda and Africa, and to tell a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate. It was an in-silico study in which intrinsic and acquired antibiotic resistance genes, and/or chromosomal resistance mutations were identified using PATRIC, CARD, NDARO and ResFinder. Screening for insertion sequences was done using ISfinder. Also, plasmid screening, phylogenetic analysis and sequence typing were performed using PlasmidFinder, PATRIC and Gubbin, and MLST respectively.The isolate belonged to the Sequence type 136, belonging to Clonal complex 208 and Global complex 2. This isolate shared close homology with strains from Tanzania. Resistance in the isolate was chromosomally and mobile genetic element-mediated by Acinetobacter-derived cephalosporinases and carbapenem hydrolyzing class D β-lactamses, blaOXA-2, 51, 5 88, 317, blaADC-2, 25. Colistin resistance was associated with previously documented mutants, lpxA and lpxC. Other key resistance genes identified were: aph(3”)-lb, aph(6)-ld, aph(3’)-la, aac(3)-lld, aac(3)-lla, aph(3’)-l, aph(3”)-l, aph(6)-lc, aph(6)-ld, aac(3)-II, III, IV, VI, VIII, IX, X, macA, macB, tetA, tetB, tetR, dfrA, and those of the floR family. RSF1010 like IncQ broad-host-range plasmids and features of pACICU1, pACICU2, and p3ABAYE Acinetobacter baumannii plasmids namely partitioning proteins ParA and B were present. Insertion sequences present included IS3, IS5, IS66 and those of the ISLre2 families.The study described for the first time a pan-drug resistant Acinetobacter baumannii from Uganda, and told a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate despite being limited by pan-drug resistance phenotypic data. It provides a basis to track trends in antibiotic resistance and identification of emerging resistance patterns in Acinetobacter baumannii in Uganda.

scholarly journals OXA-type carbapenemases in Acinetobacter baumannii in South America

2011 ◽  
Vol 6 (04) ◽  
pp. 311-316 ◽  
Author(s):  
Andrés Opazo ◽  
Mariana Domínguez ◽  
Helia Bello ◽  
Sebastian G.B. Amyes ◽  
Gerardo González-Rocha
Keyword(s):  
Intensive Care ◽  
South America ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
Opportunistic Pathogen ◽  
Class D ◽  
Different Types ◽  
Special Mention ◽  
Therapeutic Alternatives

Acinetobacter baumannii is an opportunistic pathogen that is frequently involved in outbreaks of infection, occurring mostly in intensive care units. The increasing incidence of carbapenem resistance in A. baumannii worldwide is a concern since it limits drastically the range of therapeutic alternatives. The most important mechanism of carbapenem resistance is the enzymatic hydrolysis mediated by carbapenemases. In A. baumannii these enzymes are usually OXA-type carbapenemases, and belong to class D according to the classification of Ambler. The OXA-type carbapenemases are divided into five subgroups, four of which correspond to acquired carbapenemases, which accounts for the distribution of genes blaOXA in different geographic areas. In this work we review the different types of OXA-type carbapenemases present in A. baumannii, emphasizing the current situation in South America with special mention to the findings in Chile.

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