ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance
Treatment of infections caused by ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) with carbapenem antibiotics can lead to the development of carbapenem resistance over time through the acquisition of porin mutations and plasmids bearing <i...
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MDPI AG
2025-06-01
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| author | Michelle Chioma Kalu Akanksha Acharya Peter Jorth Annie Wong-Beringer |
| author_facet | Michelle Chioma Kalu Akanksha Acharya Peter Jorth Annie Wong-Beringer |
| author_sort | Michelle Chioma Kalu |
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| description | Treatment of infections caused by ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) with carbapenem antibiotics can lead to the development of carbapenem resistance over time through the acquisition of porin mutations and plasmids bearing <i>blaKPC</i>. However, the impact of genetic background and the presence of CRISPR-Cas systems on the evolutionary path towards carbapenem resistance in EC and KP has yet to be investigated. The in-human evolution following repeated carbapenem treatment among ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) clinical pairs (n = 45 pairs) was examined to determine the relationship between strain genetic background (MLST, CRISPR-Cas) and the evolved genetic mutations related to resistance, virulence, and metabolism by whole genome sequencing. ST131 and ST258 were predominant among seven distinct STs in EC (70%, 19/27) and 11 STs in KP (33%, 6/18), respectively. Complete CRISPR-Cas systems were present in 22% EC (6/27) and 27.8% (5/18) KP pairs, but none in strains belonging to ST131 or ST258; partial loss of CRISPR-Cas was associated with increased carbapenem resistance. Porin, virulence, and metabolism-related genetic mutations were present on the chromosome in both the EC and KP evolved strains, but their presence was differentially associated with the CRISPR-Cas system. Future research on the role of antibiotic exposure in the species-specific resistance evolution of the <i>Enterobacterales</i> could guide antimicrobial stewardship efforts. |
| format | Article |
| id | doaj-art-26d4e9cc8d1c49a899012b26af55a3fc |
| institution | DOAJ |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Microorganisms |
| spelling | doaj-art-26d4e9cc8d1c49a899012b26af55a3fc2025-08-20T03:16:35ZengMDPI AGMicroorganisms2076-26072025-06-01136138710.3390/microorganisms13061387ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem ResistanceMichelle Chioma Kalu0Akanksha Acharya1Peter Jorth2Annie Wong-Beringer3Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USATitus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USADepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USATitus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USATreatment of infections caused by ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) with carbapenem antibiotics can lead to the development of carbapenem resistance over time through the acquisition of porin mutations and plasmids bearing <i>blaKPC</i>. However, the impact of genetic background and the presence of CRISPR-Cas systems on the evolutionary path towards carbapenem resistance in EC and KP has yet to be investigated. The in-human evolution following repeated carbapenem treatment among ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) clinical pairs (n = 45 pairs) was examined to determine the relationship between strain genetic background (MLST, CRISPR-Cas) and the evolved genetic mutations related to resistance, virulence, and metabolism by whole genome sequencing. ST131 and ST258 were predominant among seven distinct STs in EC (70%, 19/27) and 11 STs in KP (33%, 6/18), respectively. Complete CRISPR-Cas systems were present in 22% EC (6/27) and 27.8% (5/18) KP pairs, but none in strains belonging to ST131 or ST258; partial loss of CRISPR-Cas was associated with increased carbapenem resistance. Porin, virulence, and metabolism-related genetic mutations were present on the chromosome in both the EC and KP evolved strains, but their presence was differentially associated with the CRISPR-Cas system. Future research on the role of antibiotic exposure in the species-specific resistance evolution of the <i>Enterobacterales</i> could guide antimicrobial stewardship efforts.https://www.mdpi.com/2076-2607/13/6/1387carbapenem resistanceESBL-producing <i>Enterobacterales</i>genetic evolutionCRISPR-Cas |
| spellingShingle | Michelle Chioma Kalu Akanksha Acharya Peter Jorth Annie Wong-Beringer ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance Microorganisms carbapenem resistance ESBL-producing <i>Enterobacterales</i> genetic evolution CRISPR-Cas |
| title | ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance |
| title_full | ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance |
| title_fullStr | ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance |
| title_full_unstemmed | ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance |
| title_short | ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance |
| title_sort | esbl producing i escherichia coli i and i klebsiella pneumoniae i exhibit divergent paths during in human evolution towards carbapenem resistance |
| topic | carbapenem resistance ESBL-producing <i>Enterobacterales</i> genetic evolution CRISPR-Cas |
| url | https://www.mdpi.com/2076-2607/13/6/1387 |
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