WarA, a remote homolog of NpmA and KamB from Nocardia wallacei, confers broad spectrum aminoglycoside resistance in Nocardia and Mycobacteria
Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved..
OBJECTIVES: Aminoglycoside resistance in bacteria is typically conferred by specific drug-modifying enzymes. Infrequently, such resistance is achieved through 16S ribosomal RNA methyltransferases, such as NpmA and KamB encoded by Escherichia coli and Streptoalloteichus tenebrarius, respectively. These enzymes are not widespread and have not been described in Nocardia species to date.
METHODS: We report the genomic mining of 18 Nocardia wallacei isolates that were found to be specifically and substantially resistant to amikacin.
RESULTS: We identified a gene coding for a protein with very distant homology to NpmA and KamB. However, 3-D modeling revealed that the tertiary structure of these three proteins was highly similar. Cloning and expressing this gene in two susceptible bacteria Nocardia asteroides, and Mycobacterium smegmatis (another Actinobacterium) led to high-level, pan-aminoglycoside resistance in both cases. We named this gene warA (Wallacei Amikacin Resistance A).
CONCLUSIONS: This is the first description and experimental characterization of a gene of this family in Nocardia, and the first demonstration that such activity could lead to pan-aminoglycoside resistance in Mycobacteria as well. The discovery of this novel gene has important biotechnology and clinical implications.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
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| Enthalten in: |
International journal of antimicrobial agents - 63(2024), 2 vom: 25. Feb., Seite 107089 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hershko, Yizhak [VerfasserIn] |
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| Links: |
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| Themen: |
16S rRNA methylation |
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| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 19.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijantimicag.2024.107089 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367088673 |
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| 100 | 1 | |a Hershko, Yizhak |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a WarA, a remote homolog of NpmA and KamB from Nocardia wallacei, confers broad spectrum aminoglycoside resistance in Nocardia and Mycobacteria |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 19.02.2024 | ||
| 500 | |a Date Revised 19.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved. | ||
| 520 | |a OBJECTIVES: Aminoglycoside resistance in bacteria is typically conferred by specific drug-modifying enzymes. Infrequently, such resistance is achieved through 16S ribosomal RNA methyltransferases, such as NpmA and KamB encoded by Escherichia coli and Streptoalloteichus tenebrarius, respectively. These enzymes are not widespread and have not been described in Nocardia species to date | ||
| 520 | |a METHODS: We report the genomic mining of 18 Nocardia wallacei isolates that were found to be specifically and substantially resistant to amikacin | ||
| 520 | |a RESULTS: We identified a gene coding for a protein with very distant homology to NpmA and KamB. However, 3-D modeling revealed that the tertiary structure of these three proteins was highly similar. Cloning and expressing this gene in two susceptible bacteria Nocardia asteroides, and Mycobacterium smegmatis (another Actinobacterium) led to high-level, pan-aminoglycoside resistance in both cases. We named this gene warA (Wallacei Amikacin Resistance A) | ||
| 520 | |a CONCLUSIONS: This is the first description and experimental characterization of a gene of this family in Nocardia, and the first demonstration that such activity could lead to pan-aminoglycoside resistance in Mycobacteria as well. The discovery of this novel gene has important biotechnology and clinical implications | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 16S rRNA methylation | |
| 650 | 4 | |a Amikacin | |
| 650 | 4 | |a Aminoglycoside | |
| 650 | 4 | |a Antimicrobial resistance | |
| 650 | 4 | |a Mycobacteria | |
| 650 | 4 | |a Nocardia | |
| 650 | 7 | |a Aminoglycosides |2 NLM | |
| 650 | 7 | |a Amikacin |2 NLM | |
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| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a RNA, Ribosomal, 16S |2 NLM | |
| 700 | 1 | |a Rannon, Ella |e verfasserin |4 aut | |
| 700 | 1 | |a Adler, Amos |e verfasserin |4 aut | |
| 700 | 1 | |a Burstein, David |e verfasserin |4 aut | |
| 700 | 1 | |a Barkan, Daniel |e verfasserin |4 aut | |
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