25fedd4acf8cedd84744c8a77f4cfab0 MIS_a2025m3v13n3.pdf baba3060b9e07a9c75823c25c44c8cf42366b4e2 MIS_a2025m3v13n3.pdf f4a7c027bd83f6f63cbb68579c47b685edecf9bbfb9a8ae03aff8c7e7ed07c81 MIS_a2025m3v13n3.pdf Title: Novel PiuC, PirA, and PiuA mutations leading to in vivo cefiderocol resistance progression in IMP-16- and KPC-2-producing Pseudomonas aeruginosa from a leukemic patient Subject: Microbiol Spectr 2025.13:e01928-24 Keywords: Pseudomonas aeruginosa, carbapenem-resistant, cefiderocol, PiuA, PiuC, PirA, leukemia, Oxford Nanopore Author: Joaquim Viñes, Sabina Herrera, Andrea Vergara, Ignasi Roca, Jordi Vila, Tommaso Francesco Aiello, José Antonio Martínez, Ana del Río, Carlos Lopera, Carolina Garcia-Vidal, Climent Casals-Pascual, Àlex Soriano, Cristina Pitart Creator: Antenna House XSL Formatter V7.4 MR2 Linux : 7.4.3.63807 (2024-03-22T11:49+09) Producer: Antenna House PDF Output Library 7.4.1901; modified using iText 4.2.0 by 1T3XT CreationDate: Tue Feb 18 08:30:03 2025 CET ModDate: 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UseNone Language: EN Outlines: Item: Title: Novel PiuC, PirA, and PiuA mutations leading to in vivo cefiderocol resistance progression in IMP-16- and KPC-2-producing Pseudomonas aeruginosa from a leukemic patient Children: Item: Title: MATERIALS AND METHODS Children: Item: Title: Samples, strain identification, cefiderocol susceptibility, and carbapenemase detection Item: Title: DNA extraction and Nanopore sequencing Item: Title: Genome assembly and analysis Item: Title: RESULTS Children: Item: Title: Case history Item: Title: Genetic analysis Item: Title: DISCUSSION Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/png ImageWidth: 32 ImageHeight: 51 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 796 ImageHeight: 136 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: 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FontDescriptor: FontName: OATGZJ+MyriadPro-Light Flags: Nonsymbolic FontBBox: -153, -250, 1046, 935 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: OATGZJ+MyriadPro-Regular FontSubset: true FirstChar: 32 LastChar: 156 FontDescriptor: FontName: OATGZJ+MyriadPro-Regular Flags: Nonsymbolic FontBBox: -157, -250, 1126, 952 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: OATGZJ+MyriadPro-Semibold FontSubset: true FirstChar: 32 LastChar: 132 FontDescriptor: FontName: OATGZJ+MyriadPro-Semibold Flags: Nonsymbolic FontBBox: -161, -250, 1198, 973 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: OATGZJ+MyriadPro-SemiboldIt FontSubset: true FirstChar: 32 LastChar: 118 FontDescriptor: FontName: OATGZJ+MyriadPro-SemiboldIt Flags: Nonsymbolic, Italic FontBBox: -193, -250, 1164, 972 FontFile3: true ToUnicode: true Font: BaseFont: OATGZJ+MyriadPro-Semibold FontSubset: true FirstChar: 44 LastChar: 128 FontDescriptor: FontName: OATGZJ+MyriadPro-Semibold Flags: Nonsymbolic FontBBox: -161, -250, 1198, 973 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: OATGZJ+MyriadPro-Regular FontSubset: true FirstChar: 40 LastChar: 139 FontDescriptor: FontName: OATGZJ+MyriadPro-Regular Flags: Nonsymbolic FontBBox: -157, -250, 1126, 952 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: OATGZJ+MyriadPro-It FontSubset: true FirstChar: 32 LastChar: 120 FontDescriptor: FontName: OATGZJ+MyriadPro-It Flags: Nonsymbolic, Italic FontBBox: -185, -250, 1090, 953 FontFile3: true ToUnicode: true Font: BaseFont: OATGZJ+MyriadPro-Bold FontSubset: true FirstChar: 48 LastChar: 57 FontDescriptor: FontName: OATGZJ+MyriadPro-Bold Flags: Nonsymbolic FontBBox: -163, -250, 1256, 989 FontFile3: true ToUnicode: true XMP: application/pdfNovel PiuC, PirA, and PiuA mutations leading to in vivo cefiderocol resistance progression in IMP-16- and KPC-2-producing Pseudomonas aeruginosa from a leukemic patientSpectrum01928-24Joaquim ViñesSabina HerreraAndrea VergaraIgnasi RocaJordi VilaTommaso Francesco AielloJosé Antonio MartínezAna del RíoCarlos LoperaCarolina Garcia-VidalCliment Casals-PascualÀlex SorianoCristina PitartJoaquim ViñesSabina HerreraAndrea VergaraIgnasi RocaJordi VilaTommaso Francesco AielloJosé Antonio MartínezAna del RíoCarlos LoperaCarolina Garcia-VidalCliment Casals-PascualÀlex SorianoCristina PitartAmerican Society for MicrobiologyCopyright © 2025 Viñes et al.This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.20252023Pseudomonas aeruginosa is an opportunistic pathogen capable of causing severe infections in immunocompromised individuals, who often require prolonged antibiotic therapy. The emergence of carbapenemase-producing P. aeruginosa has further complicated the management of nosocomial infections, limiting therapeutic options. Cefiderocol has recently emerged as a promising antipseudomonal agent, using the bacterial iron transport system to gain entry into the cell; however, there have been reports of P. aeruginosa resistant to cefiderocol. We describe the in vivo cefiderocol resistance progression of four consecutive P. aeruginosa isolates from one patient with T-cell acute lymphoblastic leukemia. Analysis of potential genes involved in cefiderocol transport resulted in three genes mutated in two resistant isolates. One isolate presented a S116F substitution in PiuC, and the other presented a deletion of 29 amino acids in the signal peptide of PiuA and a STOP substitution in PirA, resulting in the deletion of a piece of the channel. These mutations increased 24- and 64-folds the cefiderocol minimum inhibitory concentration, respectively. The mutations in the aforementioned genes may directly impact siderophore internalization, thereby contributing to an elevation in the MIC of the antibiotic.20240731202412182165-0497uuid:bf66b5c2-006f-4e65-9898-b4b30478a33fuuid:e3bc77e8-36e5-4403-92b8-2db1886ec907 Antenna House PDF Output Library 7.4.1901; modified using iText 4.2.0 by 1T3XT Antenna House XSL Formatter V7.4 MR2 Linux : 7.4.3.63807 (2024-03-22T11:49+09) 2025-02-18T07:30:03+00:00 2025-11-05T00:01:45-08:00 2025-11-05T00:01:45-08:00 0d336399-b9c8-4514-8251-b504d03d9c73 1 Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Contents: CrossMarkLogoLink Rect: 505, 701, 544, 742 LastModified: D:20250218073003+00'00' Flags: Print Annotation: Subtype: Link Contents: 10.1128/spectrum.01928-24 Rect: 450, 23, 534, 32 LastModified: D:20250218073003+00'00' Flags: Print Annotation: Subtype: Link Contents: ExternalLinking Rect: 391, 47, 530, 65 LastModified: D:20250218073003+00'00' Flags: Print Annotation: Subtype: Link 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