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      Mobile Genetic Elements Harboring Antibiotic Resistance Determinants in Acinetobacter baumannii Isolates From Bolivia

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          Abstract

          Using a combination of short- and long-read DNA sequencing, we have investigated the location of antibiotic resistance genes and characterized mobile genetic elements (MGEs) in three clinical multi-drug resistant Acinetobacter baumannii. The isolates, collected in Bolivia, clustered separately with three different international clonal lineages. We found a diverse array of transposons, plasmids and resistance islands related to different insertion sequence (IS) elements, which were located in both the chromosome and in plasmids, which conferred resistance to multiple antimicrobials, including carbapenems. Carbapenem resistance might be caused by a Tn2008 carrying the bla OXA–23 gene. Some plasmids were shared between the isolates. Larger plasmids were less conserved than smaller ones and they shared some homologous regions, while others were more diverse, suggesting that these big plasmids are more plastic than the smaller ones. The genetic basis of antimicrobial resistance in Bolivia has not been deeply studied until now, and the mobilome of these A. baumannii isolates, combined with their multi-drug resistant phenotype, mirror the transfer and prevalence of MGEs contributing to the spread of antibiotic resistance worldwide and require special attention. These findings could be useful to understand the antimicrobial resistance genetics of A. baumannii in Bolivia and the difficulty in tackling these infections.

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          Most cited references25

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          Plasmids and the spread of resistance.

          Plasmids represent one of the most difficult challenge for counteracting the dissemination of antimicrobial resistance. They contribute to the spread of relevant resistance determinants, promoting horizontal gene transfer among unrelated bacteria. Undistinguishable plasmids were identified in unrelated bacterial strains isolated at huge geographically distant area, with no apparent epidemiological links. These plasmids belong to families that are largely prevalent in naturally occurring bacteria, usually carry multiple physically linked genetic determinants, conferring resistance to different classes of antibiotics simultaneously. Plasmids also harbour virulence factors and addiction systems, promoting their stability and maintenance in the bacterial host, in different environmental conditions. The characteristics of the most successful plasmids that were at the origin of the spread of carbapenemase, expanded-spectrum β-lactamase, and plasmid-mediated quinolone resistance genes are discussed in this review. Copyright © 2013 Elsevier GmbH. All rights reserved.
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            Global spread of carbapenem-resistant Acinetobacter baumannii.

            We have investigated the molecular epidemiology and distribution of carbapenemase genes in 492 imipenem-non-susceptible Acinetobacter baumannii worldwide isolates (North and Latin America, Europe, Asia, South Africa and Australia). MICs were determined by broth microdilution and Etest. The presence of carbapenemase-encoding genes was investigated by PCR. Molecular epidemiology was performed by repetitive sequence-based PCR (rep-PCR; DiversiLab), sequence-type multiplex PCR and PFGE. Imipenem non-susceptibility was associated with ISAba1 upstream of the intrinsic bla(OXA-51-like) or the acquired carbapenemase bla(OXA-23-like), bla(OXA-40-like) or bla(OXA-58-like). Isolates were grouped into eight distinct clusters including European clones I, II and III. European clone II was the largest (246 isolates) and most widespread group (USA, pan-Europe, Israel, Asia, Australia and South Africa). The global dissemination of eight carbapenem-resistant lineages illustrates the success this organism has had in epidemic spread. The acquired OXA enzymes are widely distributed but are not the sole carbapenem resistance determinant in A. baumannii.
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              ISCR elements: novel gene-capturing systems of the 21st century?

              "Common regions" (CRs), such as Orf513, are being increasingly linked to mega-antibiotic-resistant regions. While their overall nucleotide sequences show little identity to other mobile elements, amino acid alignments indicate that they possess the key motifs of IS91-like elements, which have been linked to the mobility ent plasmids in pathogenic Escherichia coli. Further inspection reveals that they possess an IS91-like origin of replication and termination sites (terIS), and therefore CRs probably transpose via a rolling-circle replication mechanism. Accordingly, in this review we have renamed CRs as ISCRs to give a more accurate reflection of their functional properties. The genetic context surrounding ISCRs indicates that they can procure 5' sequences via misreading of the cognate terIS, i.e., "unchecked transposition." Clinically, the most worrying aspect of ISCRs is that they are increasingly being linked with more potent examples of resistance, i.e., metallo-beta-lactamases in Pseudomonas aeruginosa and co-trimoxazole resistance in Stenotrophomonas maltophilia. Furthermore, if ISCR elements do move via "unchecked RC transposition," as has been speculated for ISCR1, then this mechanism provides antibiotic resistance genes with a highly mobile genetic vehicle that could greatly exceed the effects of previously reported mobile genetic mechanisms. It has been hypothesized that bacteria will surprise us by extending their "genetic construction kit" to procure and evince additional DNA and, therefore, antibiotic resistance genes. It appears that ISCR elements have now firmly established themselves within that regimen.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                13 May 2020
                2020
                : 11
                : 919
                Affiliations
                [1] 1Faculty of Medicine and Nursing, Department of Immunology, Microbiology, and Parasitology, University of the Basque Country UPV/EHU , Leioa, Spain
                [2] 2Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne , Cologne, Germany
                [3] 3German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne , Cologne, Germany
                [4] 4Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicine , Langen, Germany
                Author notes

                Edited by: Benjamin Andrew Evans, University of East Anglia, United Kingdom

                Reviewed by: Nabil Karah, Umeå University, Sweden; Andres Felipe Opazo-Capurro, University of Concepcion, Chile

                These authors have contributed equally to this work

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.00919
                7237729
                32477313
                c2f71321-4a92-434b-8e44-522cea745d9b
                Copyright © 2020 Cerezales, Xanthopoulou, Wille, Krut, Seifert, Gallego and Higgins.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 January 2020
                : 17 April 2020
                Page count
                Figures: 9, Tables: 2, Equations: 0, References: 30, Pages: 11, Words: 0
                Funding
                Funded by: Eusko Jaurlaritza 10.13039/501100003086
                Funded by: Euskal Herriko Unibertsitatea 10.13039/501100003451
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                a. baumannii,plasmids,mobile genetic elements,antimicrobial resistance,carbapenemase

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