Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates
IntroductionThe emergence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is an urgent and alarming One Health problem. This study aimed to investigate duplications of plasmid-encoded ESBL genes and their impact on antimicrobial resistance (AMR) phenotypes in clinical and screen...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1343858/full |
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| author | Annika Sobkowiak Annika Sobkowiak Natalie Scherff Franziska Schuler Stefan Bletz Alexander Mellmann Vera Schwierzeck Vincent van Almsick Vincent van Almsick |
| author_facet | Annika Sobkowiak Annika Sobkowiak Natalie Scherff Franziska Schuler Stefan Bletz Alexander Mellmann Vera Schwierzeck Vincent van Almsick Vincent van Almsick |
| author_sort | Annika Sobkowiak |
| collection | DOAJ |
| description | IntroductionThe emergence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is an urgent and alarming One Health problem. This study aimed to investigate duplications of plasmid-encoded ESBL genes and their impact on antimicrobial resistance (AMR) phenotypes in clinical and screening isolates.MethodsMulti-drug-resistant bacteria from hospitalized patients were collected during routine clinical surveillance from January 2022 to June 2023, and their antimicrobial susceptibility patterns were determined. Genotypes were extracted from long-read whole-genome sequencing data. Furthermore, plasmids and other mobile genetic elements associated with ESBL genes were characterized, and the ESBL genes were correlated to ceftazidime minimal inhibitory concentration (MIC).ResultsIn total, we identified four cases of plasmid-encoded ESBL gene duplications that match four genetically similar plasmids during the 18-month surveillance period: five Escherichia coli and three Klebsiella pneumoniae isolates. As the ESBL genes were part of transposable elements, the surrounding sequence regions were duplicated as well. In-depth analysis revealed insertion sequence (IS)-mediated transposition mechanisms. Isolates with duplicated ESBL genes exhibited a higher MIC for ceftazidime in comparison to isolates with a single gene copy (3–256 vs. 1.5–32 mg/L, respectively).ConclusionESBL gene duplications led to an increased phenotypic resistance against ceftazidime. Our data suggest that ESBL gene duplications by an IS-mediated transposition are a relevant mechanism for how AMR develops in the clinical setting and is part of the microevolution of plasmids. |
| first_indexed | 2024-03-07T21:43:00Z |
| format | Article |
| id | doaj.art-edd2e9cf3ace44a5a28e59c97ba1c126 |
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| language | English |
| last_indexed | 2024-03-07T21:43:00Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-edd2e9cf3ace44a5a28e59c97ba1c1262024-02-26T04:51:21ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-02-011410.3389/fcimb.2024.13438581343858Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolatesAnnika Sobkowiak0Annika Sobkowiak1Natalie Scherff2Franziska Schuler3Stefan Bletz4Alexander Mellmann5Vera Schwierzeck6Vincent van Almsick7Vincent van Almsick8Institute of Hygiene, University Hospital Münster, Münster, GermanyDepartment of Cardiology I – Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Münster, Münster, GermanyInstitute of Hygiene, University Hospital Münster, Münster, GermanyInstitute of Medical Microbiology, University Hospital Münster, Münster, GermanyInstitute of Hygiene, University Hospital Münster, Münster, GermanyInstitute of Hygiene, University Hospital Münster, Münster, GermanyInstitute of Hygiene, University Hospital Münster, Münster, GermanyInstitute of Hygiene, University Hospital Münster, Münster, GermanyDepartment of Cardiology I – Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Münster, Münster, GermanyIntroductionThe emergence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is an urgent and alarming One Health problem. This study aimed to investigate duplications of plasmid-encoded ESBL genes and their impact on antimicrobial resistance (AMR) phenotypes in clinical and screening isolates.MethodsMulti-drug-resistant bacteria from hospitalized patients were collected during routine clinical surveillance from January 2022 to June 2023, and their antimicrobial susceptibility patterns were determined. Genotypes were extracted from long-read whole-genome sequencing data. Furthermore, plasmids and other mobile genetic elements associated with ESBL genes were characterized, and the ESBL genes were correlated to ceftazidime minimal inhibitory concentration (MIC).ResultsIn total, we identified four cases of plasmid-encoded ESBL gene duplications that match four genetically similar plasmids during the 18-month surveillance period: five Escherichia coli and three Klebsiella pneumoniae isolates. As the ESBL genes were part of transposable elements, the surrounding sequence regions were duplicated as well. In-depth analysis revealed insertion sequence (IS)-mediated transposition mechanisms. Isolates with duplicated ESBL genes exhibited a higher MIC for ceftazidime in comparison to isolates with a single gene copy (3–256 vs. 1.5–32 mg/L, respectively).ConclusionESBL gene duplications led to an increased phenotypic resistance against ceftazidime. Our data suggest that ESBL gene duplications by an IS-mediated transposition are a relevant mechanism for how AMR develops in the clinical setting and is part of the microevolution of plasmids.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1343858/fullantimicrobial resistanceESBLplasmidtransposonsgene duplicationantibiotic susceptibility |
| spellingShingle | Annika Sobkowiak Annika Sobkowiak Natalie Scherff Franziska Schuler Stefan Bletz Alexander Mellmann Vera Schwierzeck Vincent van Almsick Vincent van Almsick Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates Frontiers in Cellular and Infection Microbiology antimicrobial resistance ESBL plasmid transposons gene duplication antibiotic susceptibility |
| title | Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates |
| title_full | Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates |
| title_fullStr | Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates |
| title_full_unstemmed | Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates |
| title_short | Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates |
| title_sort | plasmid encoded gene duplications of extended spectrum β lactamases in clinical bacterial isolates |
| topic | antimicrobial resistance ESBL plasmid transposons gene duplication antibiotic susceptibility |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1343858/full |
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