Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance
<b>Background/Objectives:</b> Carbapenem resistance poses a significant health threat. This study reports the first detection and characterization of a novel variant of New Delhi metallo-β-lactamase (<i>bla</i><sub>NDM-60</sub>) in <i>Escherichia coli</i&...
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MDPI AG
2024-12-01
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| author | Farah Al-Marzooq Akela Ghazawi Mushal Allam Timothy Collyns Aqeel Saleem |
| author_facet | Farah Al-Marzooq Akela Ghazawi Mushal Allam Timothy Collyns Aqeel Saleem |
| author_sort | Farah Al-Marzooq |
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| description | <b>Background/Objectives:</b> Carbapenem resistance poses a significant health threat. This study reports the first detection and characterization of a novel variant of New Delhi metallo-β-lactamase (<i>bla</i><sub>NDM-60</sub>) in <i>Escherichia coli</i> from the United Arab Emirates (UAE), including its genetic context and relationship to global strains. <b>Methods:</b> NDM-60-producing <i>E. coli</i> was isolated from a rectal swab during routine screening. Characterization involved whole-genome sequencing, antimicrobial susceptibility testing, and comparative genomic analysis with 66 known NDM variants. Core genome analysis was performed against 42 global <i>E. coli</i> strains, including the single other reported NDM-60-positive isolate. <b>Results:</b> The strain demonstrated extensive drug resistance, including resistance to novel β-lactam/β-lactamase inhibitor combinations, notably taniborbactam. NDM-60 differs from the closely related NDM-5 by a single amino acid substitution (Asp202Asn) and two amino acid substitutions (Val88Leu and Met154Leu) compared to NDM-1. NDM-60 is located on a nonconjugative IncX3 plasmid. The strain belongs to sequence type 940 (ST940). Phylogenetic analysis revealed high diversity among the global ST940 strains, which carry a plethora of resistance genes and originated from humans, animals, and the environment from diverse geographic locations. <b>Conclusions:</b> NDM-60 emergence in the UAE represents a significant evolution in carbapenemase diversity. Its presence on a nonconjugative plasmid may limit spread; however, its extensive resistance profile is concerning. Further studies are needed to determine the prevalence, dissemination, and clinical impact of NDM-60. NDM evolution underscores the ongoing challenge in managing antimicrobial resistance and the critical importance of vigilant molecular surveillance. It also highlights the pressing demand to discover new antibiotics to fight resistant bacteria. |
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| institution | DOAJ |
| issn | 2079-6382 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Antibiotics |
| spelling | doaj-art-94d5fa05b1cf4f7fa544270ef2e70a0f2025-08-20T02:53:18ZengMDPI AGAntibiotics2079-63822024-12-011312115810.3390/antibiotics13121158Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial ResistanceFarah Al-Marzooq0Akela Ghazawi1Mushal Allam2Timothy Collyns3Aqeel Saleem4Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab EmiratesDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab EmiratesDepartment of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab EmiratesTawam Hospital, Al Ain P.O. Box 5674, United Arab EmiratesTawam Hospital, Al Ain P.O. Box 5674, United Arab Emirates<b>Background/Objectives:</b> Carbapenem resistance poses a significant health threat. This study reports the first detection and characterization of a novel variant of New Delhi metallo-β-lactamase (<i>bla</i><sub>NDM-60</sub>) in <i>Escherichia coli</i> from the United Arab Emirates (UAE), including its genetic context and relationship to global strains. <b>Methods:</b> NDM-60-producing <i>E. coli</i> was isolated from a rectal swab during routine screening. Characterization involved whole-genome sequencing, antimicrobial susceptibility testing, and comparative genomic analysis with 66 known NDM variants. Core genome analysis was performed against 42 global <i>E. coli</i> strains, including the single other reported NDM-60-positive isolate. <b>Results:</b> The strain demonstrated extensive drug resistance, including resistance to novel β-lactam/β-lactamase inhibitor combinations, notably taniborbactam. NDM-60 differs from the closely related NDM-5 by a single amino acid substitution (Asp202Asn) and two amino acid substitutions (Val88Leu and Met154Leu) compared to NDM-1. NDM-60 is located on a nonconjugative IncX3 plasmid. The strain belongs to sequence type 940 (ST940). Phylogenetic analysis revealed high diversity among the global ST940 strains, which carry a plethora of resistance genes and originated from humans, animals, and the environment from diverse geographic locations. <b>Conclusions:</b> NDM-60 emergence in the UAE represents a significant evolution in carbapenemase diversity. Its presence on a nonconjugative plasmid may limit spread; however, its extensive resistance profile is concerning. Further studies are needed to determine the prevalence, dissemination, and clinical impact of NDM-60. NDM evolution underscores the ongoing challenge in managing antimicrobial resistance and the critical importance of vigilant molecular surveillance. It also highlights the pressing demand to discover new antibiotics to fight resistant bacteria.https://www.mdpi.com/2079-6382/13/12/1158<i>Escherichia coli</i>whole-genome sequencingNew Delhi metallo-β-lactamaseNDM-60carbapenem resistanceUnited Arab Emirates |
| spellingShingle | Farah Al-Marzooq Akela Ghazawi Mushal Allam Timothy Collyns Aqeel Saleem Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance Antibiotics <i>Escherichia coli</i> whole-genome sequencing New Delhi metallo-β-lactamase NDM-60 carbapenem resistance United Arab Emirates |
| title | Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance |
| title_full | Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance |
| title_fullStr | Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance |
| title_full_unstemmed | Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance |
| title_short | Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i><sub>NDM-60</sub>) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance |
| title_sort | novel variant of new delhi metallo beta lactamase i bla i sub ndm 60 sub discovered in a clinical strain of i escherichia coli i from the united arab emirates an emerging challenge in antimicrobial resistance |
| topic | <i>Escherichia coli</i> whole-genome sequencing New Delhi metallo-β-lactamase NDM-60 carbapenem resistance United Arab Emirates |
| url | https://www.mdpi.com/2079-6382/13/12/1158 |
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