scholarly journals Genomic Analysis of Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Major Endemic Clones in South America

2020 ◽  
Vol 11 ◽  
Author(s):  
Carolina Silva Nodari ◽  
Rodrigo Cayô ◽  
Ana Paula Streling ◽  
Felipe Lei ◽  
Julia Wille ◽  
...  
Keyword(s):  
South America ◽  
Acinetobacter Baumannii ◽  
Outer Membrane Proteins ◽  
Acquired Resistance ◽  
Clinical Isolates ◽  
Efflux System ◽  
Illumina Platform ◽  
Synonymous Mutations ◽  
Resistance Determinants ◽  
Carbapenem Resistant

Carbapenem-resistant Acinetobacter baumannii (CRAB) are emerging worldwide. In South America, clinical isolates presenting such a phenotype usually do not belong to the globally distributed international clone 2 (IC2). The majority of these isolates are also resistant to multiple other antimicrobials and are often designated extremely drug-resistant (XDR). The aim of this study was to characterize the resistance mechanisms presented by 18 carbapenem-resistant A. baumannii isolates from five different Brazilian hospitals. Species identification was determined by rpoB sequencing, and antimicrobial susceptibility was determined by broth microdilution. Isolates were submitted to whole genome sequencing using Illumina platform and genetic similarity was determined by PFGE, MLST, and cgMLST. Genome analysis was used to identify intrinsic and acquired resistance determinants, including mutations in the AdeRSABC efflux system and in outer membrane proteins (OMPs). All isolates were identified as A. baumannii and grouped into 4 pulsotypes by PFGE, which belonged to clonal complexes (CC) 15Pas/103Ox (n = 4) and 79Pas/113Ox (n = 14), corresponding to IC4 and IC5, respectively. High MIC values to carbapenems, broad-spectrum cephalosporins, amikacin, and ciprofloxacin were observed in all isolates, while MICs of ampicillin/sulbactam, gentamicin, and tigecycline varied among the isolates. Minocycline was the most active antimicrobial agent tested. Moreover, 12 isolates (66.7%) were considered resistant to polymyxins. Besides intrinsic OXA-51 and ADC variants, all isolates harbored an acquired carbapenem-hydrolyzing class D β-lactamase (CHDL) encoding gene, either blaOXA–23 or blaOXA–72. A diversity of aminoglycoside modifying enzymes and resistance determinants to other antimicrobial classes were found, as well as mutations in gyrA and parC. Non-synonymous mutations have also been identified in the AdeRSABC efflux system and in most OMPs, but they were considered natural polymorphisms. Moreover, resistance to polymyxins among isolates belonging to IC5 were associated to non-synonymous mutations in pmrB, but no known polymyxin resistance mechanism was identified in isolates belonging to IC4. In conclusion, A. baumannii clinical isolates belonging to South America’s major clones present a myriad of antimicrobial resistance determinants. Special attention should be paid to natural polymorphisms observed in each clonal lineage, especially regarding non-synonymous mutations in constitutive genes associated with distinct resistance phenotypes.

scholarly journals Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates from Egyptian Patients

2020 ◽  
Author(s):  
Reem M Hassan ◽  
Sherifa T Salem ◽  
Saly Ismail Mostafa Hassan ◽  
Asmaa Sayed Hegab ◽  
Yasmine S Elkholy
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Common Mechanism ◽  
Carbapenem Resistant ◽  
Egyptian Patients ◽  
Global Threat

AbstractAcinetobacter baumannii (A. baumannii) represents a global threat owing to its ability to resist most of the currently available antimicrobial agents. Moreover, emergence of carbapenem resistant A. baumannii (CR-AB) isolates limits the available treatment options. Enzymatic degradation by variety of ß-lactamases, have been identified as the most common mechanism of carbapenem resistance in A. baumannii. The alarming increase in the prevalence of CR-AB necessitates continuous screening and molecular characterization to appreciate the problem. The present study was performed to assess the prevalence and characterize carbapenemases among 206 CR-AB isolated from various clinical specimens collected from different intensive care units at Kasr Al-Aini Hospital.All isolates were confirmed to be A. baumannii by detection of the blaOXA-51-like gene. Molecular screening of 13 common Ambler class bla carbapenemases genes in addition to insertion sequence (IS-1) upstream OXA-23 was performed by using four sets of multiplex PCR, followed by identification using gene sequencing technology. Among the investigated genes, the prevalence of blaOXA-23, and blaOXA-58 were 77.7%, and 1.9%, respectively. The ISAba1 was detected in 10% of the blaOXA-23 positive isolates. The prevalence of metallo-β-lactamases (MBLs) studied; blaNDM-1, blaSPM, blaVIM, blaSIM-1 were 11.7%, 6.3%, 0.5%, and 0.5% respectively. One of class A; bla KPC was detected in 10.7% of the investigated isolates. blaOXA-24/40, blaIMP, blaGES, blaVEB and blaGIM were not detected in any of the studied isolates. Moreover, 18.4% of the isolates have shown to harbor two or more of the screened bla genes. We concluded that the most prevalent type of ß-lactamases genes among CR-AB isolates collected from Egyptian patients were blaOXA-23 followed by blaNDM-1 and blaKPC.Author summaryCarbapenem-resistant A. baumannii has become a real global health threat. The aim of the present study was to characterize and to assess the prevalence of carbapenemases among 206 CR-AB clinical isolates from Egyptian patients. We concluded that the most prevalent type of ß-lactamases genes among CR-AB isolates collected from Egyptian patients were blaOXA-23 followed by blaNDM-1 and blaKPC. In this study, ISAba1 was detected upstream 10% of blaOXA-23 positive isolates only which indicates that the spread of resistance among Acinetobacter isolates could be either chromosomal or plamid-mediated.

scholarly journals Colistin heteroresistance in carbapenem-resistant Acinetobacter baumannii clinical isolates from a Thai university hospital

2020 ◽  
Vol 36 (7) ◽  
Author(s):  
Khin Thet Thet ◽  
Kamonwan Lunha ◽  
Arpasiri Srisrattakarn ◽  
Aroonlug Lulitanond ◽  
Ratree Tavichakorntrakool ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Isolates ◽  
University Hospital ◽  
Carbapenem Resistant ◽  
Thai University

scholarly journals The Capsular Polysaccharide of Acinetobacter baumannii Is an Obstacle for Therapeutic Passive Immunization Strategies

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Shun Xin Wang-Lin ◽  
Ruth Olson ◽  
Janet M. Beanan ◽  
Ulrike MacDonald ◽  
Joseph P. Balthasar ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Outer Membrane ◽  
Bactericidal Activity ◽  
Capsular Polysaccharide ◽  
Rapid Development ◽  
Outer Membrane Proteins ◽  
Passive Immunization ◽  
Clinical Isolates ◽  
Content Type ◽  
Resistant Strains

ABSTRACT Acinetobacter baumannii has become an important concern for human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from A. baumannii infection, but monoclonal anti-OMP antibodies have not been developed, and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (MAbs) targeting outer membrane protein A (OmpA) of A. baumannii. Five anti-OmpA MAbs were developed using hybridoma technology and showed strong binding to strain ATCC 19606. However, low antibody binding was observed when they were tested against six clinical isolates, which included extensively drug-resistant strains. In contrast, high binding to an isogenic K1 capsule-negative mutant (AB307.30) was shown, suggesting that capsular polysaccharide mediated the inhibition of MAb binding to OmpA. Anti-OmpA MAbs increased the macrophage-mediated bactericidal activity of AB307.30 but failed to increase phagocytic killing of capsule-positive strains. Capsular polysaccharide was also protective against complement-mediated bactericidal activity in human ascites in the presence and absence of opsonization. Lastly, passive immunization with anti-OmpA MAbs did not confer protection against challenge with AB307-0294, the encapsulated parent strain of AB307.30, in a mouse sepsis infection model. These results reveal the important role of capsule polysaccharide in shielding OmpA and thereby inhibiting anti-OmpA MAb binding to clinical isolates. This property of capsule hindered the therapeutic utility of anti-OmpA MAbs, and it may apply to other conserved epitopes in A. baumannii.

scholarly journals Distinct Mechanisms of Dissemination of NDM-1 Metallo-β-Lactamase in Acinetobacter Species in Argentina

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Mark D. Adams ◽  
Fernando Pasteran ◽  
German M. Traglia ◽  
Jasmine Martinez ◽  
Fanny Huang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Gene ◽  
Genome Sequencing ◽  
Acinetobacter Species ◽  
Content Type ◽  
Resistance Determinants ◽  
Carbapenem Resistant ◽  
Gene Island

ABSTRACT A 4-year surveillance of carbapenem-resistant Acinetobacter spp. isolates in Argentina identified 40 strains carrying blaNDM-1. Genome sequencing revealed that most were Acinetobacter baumannii, whereas seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. blaNDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non-A. baumannii strains. A resistance gene island carrying blaPER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains.

scholarly journals Population Structure Analysis of Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates from Brazil Reveals Predominance of Clonal Complexes 1, 15, and 79

2016 ◽  
Vol 60 (4) ◽  
pp. 2545-2547 ◽  
Author(s):  
Carlos Henrique Camargo ◽  
Monique Ribeiro Tiba ◽  
Marta Regina Saes ◽  
Francielli Mahnic de Vasconcellos ◽  
Luis Fernando dos Santos ◽  
...  
Keyword(s):  
Population Structure ◽  
Acinetobacter Baumannii ◽  
Gel Electrophoresis ◽  
Multilocus Sequence Typing ◽  
Clonal Complex ◽  
Pulsed Field Gel Electrophoresis ◽  
Clinical Isolates ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Population Structure Analysis

ABSTRACTThe population structure of 71 carbapenem-resistantAcinetobacter baumanniiclinical isolates from several hospitals in Brazil was investigated by ApaI pulsed-field gel electrophoresis,blaOXA-51-like subtyping, and multilocus sequence typing (Institute Pasteur scheme). In addition to the predominance of strains carryingblaOXA-23, we detected the presence ofblaOXA-72andblaOXA-231. We observed a predominance of clonal complex 1 (CC1), CC15, and CC79 and representative strains of the worldwide-disseminated international clone I.

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