دورية أكاديمية
أعرض في EDS

Gonococcal resistance to zoliflodacin could emerge via transformation from commensal Neisseria species. An in-vitro transformation study.

التفاصيل البيبلوغرافية
العنوان: Gonococcal resistance to zoliflodacin could emerge via transformation from commensal Neisseria species. An in-vitro transformation study.
المؤلفون: Abdellati S; STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Laumen JGE; STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Laboratory of Medical Microbiology, University of Antwerp, Wilrijk, Belgium., de Block T; Clinical Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., De Baetselier I; Clinical Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Van Den Bossche D; Clinical Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Van Dijck C; STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Laboratory of Medical Microbiology, University of Antwerp, Wilrijk, Belgium., Manoharan-Basil SS; STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. sbasil@itg.be., Kenyon C; STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Division of Infectious Diseases and HIV Medicine, University of Cape Town, Cape Town, South Africa.
المصدر: Scientific reports [Sci Rep] 2024 Jan 12; Vol. 14 (1), pp. 1179. Date of Electronic Publication: 2024 Jan 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Gonorrhea* , Oxazolidinones* , Quinolones*/pharmacology , Barbiturates* , Isoxazoles* , Morpholines* , Spiro Compounds*, Humans ; Neisseria/genetics ; Neisseria gonorrhoeae ; Microbial Sensitivity Tests ; DNA ; Anti-Bacterial Agents/pharmacology
مستخلص: One of the most promising new treatments for gonorrhoea currently in phase 3 clinical trials is zoliflodacin. Studies have found very little resistance to zoliflodacin in currently circulating N. gonorrhoeae strains, and in-vitro experiments demonstrated that it is difficult to induce resistance. However, zoliflodacin resistance may emerge in commensal Neisseria spp., which could then be transferred to N. gonorrhoeae via transformation. In this study, we investigated this commensal-resistance-pathway hypothesis for zoliflodacin. To induce zoliflodacin resistance, ten wild-type susceptible isolates belonging to 5 Neisseria species were serially passaged for up to 48 h on gonococcal agar plates containing increasing zoliflodacin concentrations. Within 7 to 10 days, all strains except N. lactamica, exhibited MICs of ≥ 4 µg/mL, resulting in MIC increase ranging from 8- to 64-fold. The last passaged strains and their baseline were sequenced. We detected mutations previously reported to cause zoliflodacin resistance in GyrB (D429N and S467N), novel mutations in the quinolone resistance determining region (QRDR) (M464R and T472P) and mutations outside the QRDR at amino acid positions 28 and 29 associated with low level resistance (MIC 2 µg/mL). Genomic DNA from the laboratory evolved zoliflodacin-resistant strains was transformed into the respective baseline wild-type strain, resulting in MICs of ≥ 8 µg/mL in most cases. WGS of transformants with decreased zoliflodacin susceptibility revealed presence of the same zoliflodacin resistance determinants as observed in the donor strains. Two inter-species transformation experiments were conducted to investigate whether zoliflodacin resistance determinants of commensal Neisseria spp. could be acquired by N. gonorrhoeae. N. gonorrhoeae strain WHO P was exposed to (i) pooled genomic DNA from the two resistant N. mucosa strains and (ii) a gyrB amplicon of the resistant N. subflava strain 45/1_8. Transformants of both experiments exhibited an MIC of 2 µg/mL and whole genome analysis revealed uptake of the mutations detected in the donor strains. This is the first in-vitro study to report that zoliflodacin resistance can be induced in commensal Neisseria spp. and subsequently transformed into N. gonorrhoeae.
(© 2024. The Author(s).)
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المشرفين على المادة: FWL2263R77 (zoliflodacin)
0 (Oxazolidinones)
0 (Quinolones)
9007-49-2 (DNA)
0 (Anti-Bacterial Agents)
0 (Barbiturates)
0 (Isoxazoles)
0 (Morpholines)
0 (Spiro Compounds)
تواريخ الأحداث: Date Created: 20240112 Date Completed: 20240115 Latest Revision: 20240116
رمز التحديث: 20240116
مُعرف محوري في PubMed: PMC10786824
DOI: 10.1038/s41598-023-49943-z
PMID: 38216602
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-023-49943-z