Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae
Cefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 c...
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| Format: | Article |
| Language: | English |
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Centers for Disease Control and Prevention
2025-01-01
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| Series: | Emerging Infectious Diseases |
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| Online Access: | https://wwwnc.cdc.gov/eid/article/31/1/24-1426_article |
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| author | Riccardo Polani Alice De Francesco Dario Tomolillo Irene Artuso Michele Equestre Rita Trirocco Gabriele Arcari Guido Antonelli Laura Villa Gianni Prosseda Paolo Visca Alessandra Carattoli |
| author_facet | Riccardo Polani Alice De Francesco Dario Tomolillo Irene Artuso Michele Equestre Rita Trirocco Gabriele Arcari Guido Antonelli Laura Villa Gianni Prosseda Paolo Visca Alessandra Carattoli |
| author_sort | Riccardo Polani |
| collection | DOAJ |
| description |
Cefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 coresident plasmids: pKpQIL, carrying variants of blaKPC carbapenemase gene, and pKPN, carrying the ferric citrate transport (FEC) system. We observed increasing FDC MICs in an Escherichia coli model system carrying different natural pKpQIL plasmids, encoding different K. pneumoniae carbapenemase (KPC) variants, in combination with a conjugative low copy number vector carrying the fec gene cluster from pKPN. We observed transcriptional repression of fiu, cirA, fepA, and fhuA siderophore receptor genes in blaKPC–fec–E. coli cells treated with ferric citrate. Screening of 27,793 K. pneumoniae whole-genome sequences revealed that the fec cluster occurs frequently in some globally distributed different KPC-producing K. pneumoniae clones (sequence types 258, 14, 45, and 512), contributing to reduced FDC susceptibility.
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| format | Article |
| id | doaj-art-3923f736064e45a7a29e07994ac7bc15 |
| institution | Kabale University |
| issn | 1080-6040 1080-6059 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Centers for Disease Control and Prevention |
| record_format | Article |
| series | Emerging Infectious Diseases |
| spelling | doaj-art-3923f736064e45a7a29e07994ac7bc152024-12-23T13:52:36ZengCenters for Disease Control and PreventionEmerging Infectious Diseases1080-60401080-60592025-01-0131112312410.3201/eid3101.241426Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniaeRiccardo PolaniAlice De FrancescoDario TomolilloIrene ArtusoMichele EquestreRita TriroccoGabriele ArcariGuido AntonelliLaura VillaGianni ProssedaPaolo ViscaAlessandra Carattoli Cefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 coresident plasmids: pKpQIL, carrying variants of blaKPC carbapenemase gene, and pKPN, carrying the ferric citrate transport (FEC) system. We observed increasing FDC MICs in an Escherichia coli model system carrying different natural pKpQIL plasmids, encoding different K. pneumoniae carbapenemase (KPC) variants, in combination with a conjugative low copy number vector carrying the fec gene cluster from pKPN. We observed transcriptional repression of fiu, cirA, fepA, and fhuA siderophore receptor genes in blaKPC–fec–E. coli cells treated with ferric citrate. Screening of 27,793 K. pneumoniae whole-genome sequences revealed that the fec cluster occurs frequently in some globally distributed different KPC-producing K. pneumoniae clones (sequence types 258, 14, 45, and 512), contributing to reduced FDC susceptibility. https://wwwnc.cdc.gov/eid/article/31/1/24-1426_articleKlebsiella pneumoniaecarbapenemase-producing Klebsiella pneumoniaeKPCcefiderocolantimicrobial resistancesiderophore |
| spellingShingle | Riccardo Polani Alice De Francesco Dario Tomolillo Irene Artuso Michele Equestre Rita Trirocco Gabriele Arcari Guido Antonelli Laura Villa Gianni Prosseda Paolo Visca Alessandra Carattoli Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae Emerging Infectious Diseases Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae KPC cefiderocol antimicrobial resistance siderophore |
| title | Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae |
| title_full | Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae |
| title_fullStr | Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae |
| title_full_unstemmed | Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae |
| title_short | Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae |
| title_sort | cefiderocol resistance conferred by plasmid located ferric citrate transport system in kpc producing klebsiella pneumoniae |
| topic | Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae KPC cefiderocol antimicrobial resistance siderophore |
| url | https://wwwnc.cdc.gov/eid/article/31/1/24-1426_article |
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