دورية أكاديمية
Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin.
| العنوان: | Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin. |
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| المؤلفون: | Egge SL; Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.; Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA.; Department of Medicine, Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA., Rizvi SA; Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.; Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA., Simar SR; UTHealth Houston School of Public Health, University of Texas Health Science Center, Houston, Texas, USA., Alcalde M; Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clinica Alemana, Universidad del Desarrollo and Multidisciplinary Initiative for Collaborative Research On Bacterial Resistance (MICROB-R), Santiago, Chile.; Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen Macarena, CSIC, Universidad de Sevilla, Seville, Spain., Martinez JRW; Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clinica Alemana, Universidad del Desarrollo and Multidisciplinary Initiative for Collaborative Research On Bacterial Resistance (MICROB-R), Santiago, Chile., Hanson BM; UTHealth Houston School of Public Health, University of Texas Health Science Center, Houston, Texas, USA., Dinh AQ; Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.; Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA., Baptista RP; Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.; Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA.; Department of Medicine, Weill Cornell Medical College, New York, New York, USA., Tran TT; Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.; Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA.; Department of Medicine, Weill Cornell Medical College, New York, New York, USA., Shelburne SA; Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA., Munita JM; Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clinica Alemana, Universidad del Desarrollo and Multidisciplinary Initiative for Collaborative Research On Bacterial Resistance (MICROB-R), Santiago, Chile., Arias CA; Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.; Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA.; Department of Medicine, Weill Cornell Medical College, New York, New York, USA., Hakki M; Department of Medicine, Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA., Miller WR; Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.; Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA.; Department of Medicine, Weill Cornell Medical College, New York, New York, USA. |
| المصدر: | Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 Aug 07; Vol. 68 (8), pp. e0012724. Date of Electronic Publication: 2024 Jul 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, American Society for Microbiology |
| مواضيع طبية MeSH: | Pseudomonas aeruginosa*/genetics , Pseudomonas aeruginosa*/drug effects , Microbial Sensitivity Tests* , Anti-Bacterial Agents*/pharmacology , Mutation* , Bacterial Proteins*/genetics , Cefiderocol*, Humans ; Cephalosporins/pharmacology ; Membrane Proteins/genetics ; Pseudomonas Infections/microbiology ; Pseudomonas Infections/drug therapy ; Drug Resistance, Bacterial/genetics |
| مستخلص: | The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR , pirS , pirA , piuA , or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates ( n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance. Competing Interests: W.R.M. has received grant support from Merck and royalties from UpToDate. C.A.A. has received royalties from UpToDate. All other authors have no conflicts to disclose. |
| التعليقات: | Update of: bioRxiv. 2024 Jan 31:2024.01.30.578008. doi: 10.1101/2024.01.30.578008. (PMID: 38352536) |
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| معلومات مُعتمدة: | P01 AI152999 United States AI NIAID NIH HHS; T32 AI141349 United States AI NIAID NIH HHS; AI134637 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI141349 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); K24 AI121296 United States AI NIAID NIH HHS; AI148342 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); AI175821 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R01 AI148342 United States AI NIAID NIH HHS; AI121296 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R01 AI134637 United States AI NIAID NIH HHS; AI152999 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R21 AI175821 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: Gram-negative resistance; Pseudomonas aeurginosa; TonB-dependent receptor; beta-lactamases; cefiderocol; heteroresistance; multi-drug resistance |
| المشرفين على المادة: | 0 (Anti-Bacterial Agents) 0 (Bacterial Proteins) SZ34OMG6E8 (Cefiderocol) 0 (Cephalosporins) 0 (Membrane Proteins) 0 (tonB protein, Bacteria) |
| تواريخ الأحداث: | Date Created: 20240712 Date Completed: 20240807 Latest Revision: 20240809 |
| رمز التحديث: | 20240809 |
| مُعرف محوري في PubMed: | PMC11304687 |
| DOI: | 10.1128/aac.00127-24 |
| PMID: | 38995033 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-6596 |
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| DOI: | 10.1128/aac.00127-24 |