دورية أكاديمية

Endolysin NC5 improves early cloxacillin treatment in a mouse model of Streptococcus uberis mastitis.

التفاصيل البيبلوغرافية
العنوان: Endolysin NC5 improves early cloxacillin treatment in a mouse model of Streptococcus uberis mastitis.
المؤلفون: Vander Elst N; Laboratory of Gene Technology, Department of Biosystems, Faculty of Bioscience Engineering, KU Leuven, Kasteelpark Arenberg 21, 3001, Heverlee, Belgium. Niels.VanderElst@ugent.be.; Laboratory of Applied Biotechnology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Valentin Vaerwyckweg 1, 9000, Ghent, Belgium. Niels.VanderElst@ugent.be.; Laboratory of Biochemistry, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Niels.VanderElst@ugent.be., Bellemans J; Laboratory of Applied Biotechnology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Valentin Vaerwyckweg 1, 9000, Ghent, Belgium.; Laboratory of Biochemistry, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium., Lavigne R; Laboratory of Gene Technology, Department of Biosystems, Faculty of Bioscience Engineering, KU Leuven, Kasteelpark Arenberg 21, 3001, Heverlee, Belgium., Briers Y; Laboratory of Applied Biotechnology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Valentin Vaerwyckweg 1, 9000, Ghent, Belgium., Meyer E; Laboratory of Biochemistry, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Evelyne.Meyer@ugent.be.
المصدر: Applied microbiology and biotechnology [Appl Microbiol Biotechnol] 2024 Dec; Vol. 108 (1), pp. 118. Date of Electronic Publication: 2024 Jan 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer International Country of Publication: Germany NLM ID: 8406612 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0614 (Electronic) Linking ISSN: 01757598 NLM ISO Abbreviation: Appl Microbiol Biotechnol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Berlin ; New York : Springer International, c1984-
مواضيع طبية MeSH: Streptococcal Infections*/drug therapy , Streptococcal Infections*/veterinary , Mastitis, Bovine*/drug therapy , Streptococcus* , Endopeptidases*, Female ; Animals ; Cattle ; Mice ; Cloxacillin/therapeutic use ; Lactation ; Disease Models, Animal
مستخلص: Streptococcus uberis frequently causes bovine mastitis, an infectious udder disease with significant economic implications for dairy cows. Conventional antibiotics, such as cloxacillin, sometimes have limited success in eliminating S. uberis as a stand-alone therapy. To address this challenge, the study objective was to investigate the VersaTile engineered endolysin NC5 as a supplemental therapy to cloxacillin in a mouse model of bovine S. uberis mastitis. NC5 was previously selected based on its intracellular killing and biofilm eradicating activity. To deliver preclinical proof-of-concept of this supplemental strategy, lactating mice were intramammarily infected with a bovine S. uberis field isolate and subsequently treated with cloxacillin (30.0 μg) combined with either a low (23.5 μg) or high (235.0 μg) dose of NC5. An antibiotic monotherapy group, as well as placebo treatment, was included as controls. Two types of responders were identified: fast (n = 17), showing response after 4-h treatment, and slow (n = 10), exhibiting no clear response at 4 h post-treatment across all groups. The high-dose combination therapy in comparison with placebo treatment impacted the hallmarks of mastitis in the fast responders by reducing (i) the bacterial load 13,000-fold (4.11 ± 0.78 Δlog 10 ; p < 0.001), (ii) neutrophil infiltration 5.7-fold (p > 0.05), and (iii) the key pro-inflammatory chemokine IL-8 13-fold (p < 0.01). These mastitis hallmarks typically followed a dose response dependent on the amount of endolysin added. The current in vivo study complements our in vitro data and provides preclinical proof-of-concept of NC5 as an adjunct to intramammary cloxacillin treatment. KEY POINTS: • Engineered endolysin NC5 was preclinically evaluated as add-on to cloxacillin treatment. • Two types of mice (slow and fast responding) were observed. • The add-on treatment decreased bacterial load, neutrophil influx, and pro-inflammatory mediators.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 1.S.236.20N Fonds Wetenschappelijk Onderzoek
فهرسة مساهمة: Keywords: Bovine mastitis; Cloxacillin; Endolysin; Mouse model; Penicillin; Streptococcus uberis
المشرفين على المادة: O6X5QGC2VB (Cloxacillin)
EC 3.4.99.- (endolysin)
EC 3.4.- (Endopeptidases)
SCR Organism: Streptococcus uberis
تواريخ الأحداث: Date Created: 20240111 Date Completed: 20240112 Latest Revision: 20240119
رمز التحديث: 20240119
مُعرف محوري في PubMed: PMC10781846
DOI: 10.1007/s00253-023-12820-w
PMID: 38204128
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-0614
DOI:10.1007/s00253-023-12820-w