Rooney, CM, Sheppard, AE, Clark, E et al. (7 more authors) (2019) Dissemination of multiple carbapenem resistance genes in an in vitro gut model simulating the human colon. The Journal of Antimicrobial Chemotherapy, 74 (7). pp. 1876-1883. ISSN 0305-7453
Abstract
Background: Carbapenemase-producing Enterobacteriaceae (CPE) pose a major global health risk. Mobile genetic elements account for much of the increasing CPE burden.
Objectives: To investigate CPE colonization and the impact of antibiotic exposure on subsequent resistance gene dissemination within the gut microbiota using a model to simulate the human colon.
Methods: Gut models seeded with CPE-negative human faeces [screened with BioMérieux chromID® CARBA-SMART (Carba-Smart), Cepheid Xpert® Carba-R assay (XCR)] were inoculated with distinct carbapenemase-producing Klebsiella pneumoniae strains (KPC, NDM) and challenged with imipenem or piperacillin/tazobactam then meropenem. Resistant populations were enumerated daily on selective agars (Carba-Smart); CPE genes were confirmed by PCR (XCR, Check-Direct CPE Screen for BD MAX™). CPE gene dissemination was tracked using PacBio long-read sequencing.
Results: CPE populations increased during inoculation, plateauing at ∼105 log10 cfu/mL in both models and persisting throughout the experiments (>65 days), with no evidence of CPE ‘washout’. After antibiotic administration, there was evidence of interspecies plasmid transfer of blaKPC-2 (111 742 bp IncFII/IncR plasmid, 99% identity to pKpQIL-D2) and blaNDM-1 (∼170 kb IncFIB/IncFII plasmid), and CPE populations rose from <0.01% to >45% of the total lactose-fermenting populations in the KPC model. Isolation of a blaNDM-1K. pneumoniae with one chromosomal single-nucleotide variant compared with the inoculated strain indicated clonal expansion within the model. Antibiotic administration exposed a previously undetected K. pneumoniae encoding blaOXA-232 (KPC model).
Conclusions: CPE exposure can lead to colonization, clonal expansion and resistance gene transfer within intact human colonic microbiota. Furthermore, under antibiotic selective pressure, new resistant populations emerge, emphasizing the need to control exposure to antimicrobials.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2019. This is an author produced version of an article published in the Journal of Antimicrobial Chemistry. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | antibiotics; polymerase chain reaction; plasmids; chromosomes; feces; genes; imipenem interspersed repetitive sequences; klebsiella pneumoniae; lactose; nucleotides; vaccination; world health; colon; meropenem; piperacillin/tazobactam; antimicrobials; microbial colonization; transfer technique; microbiome; beta-lactamase ndm-1; resistance genes; clonal expansion; carbapenem resistance; carbapenem-resistant enterobacteriaceae |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Molecular Gastroenterology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Jun 2019 15:24 |
Last Modified: | 15 Apr 2020 00:39 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/jac/dkz106 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147003 |