التفاصيل البيبلوغرافية
| العنوان: |
Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin. |
| المؤلفون: |
Egge SL, Rizvi SA, Simar SR, Alcalde M, Martinez JRW, Hanson BM, Dinh AQ, Baptista RP, Tran TT, Shelburne SA, Munita JM, Arias CA, Hakki M, Miller WR |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 31. Date of Electronic Publication: 2024 Jan 31. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| 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 4 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. |
| التعليقات: |
Update in: Antimicrob Agents Chemother. 2024 Aug 7;68(8):e0012724. doi: 10.1128/aac.00127-24. (PMID: 38995033) |
| معلومات مُعتمدة: |
K24 AI121296 United States AI NIAID NIH HHS; P01 AI152999 United States AI NIAID NIH HHS; R01 AI148342 United States AI NIAID NIH HHS; R21 AI151536 United States AI NIAID NIH HHS |
| تواريخ الأحداث: |
Date Created: 20240214 Latest Revision: 20240807 |
| رمز التحديث: |
20240807 |
| مُعرف محوري في PubMed: |
PMC10862867 |
| DOI: |
10.1101/2024.01.30.578008 |
| PMID: |
38352536 |
| قاعدة البيانات: |
MEDLINE |
