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Endolysin NC5 improves early cloxacillin treatment in a mouse model of Streptococcus uberis mastitis
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Endolysin NC5 improves early cloxacillin treatment in a mouse model of Streptococcus uberis mastitis
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Journal Article
Endolysin NC5 improves early cloxacillin treatment in a mouse model of Streptococcus uberis mastitis
2024
Overview
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.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
Subject
/ Bacteria
/ biofilm
/ Biofilms
/ Biomedical and Life Sciences
/ Biotechnologically Relevant Enzymes and Proteins
/ Cattle
/ Cloxacillin - therapeutic use
/ Enzymes
/ Female
/ Identification and classification
/ Mastitis
/ Mastitis, Bovine - drug therapy
/ Mice
/ Microbial Genetics and Genomics
/ Placebos
/ Streptococcal Infections - drug therapy
/ Streptococcal Infections - veterinary
/ Therapy
/ Udder
/ udders
