Anti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo

<i>Staphylococcus aureus</i> is a causative agent of bovine mastitis, capable of causing significant economic losses to the dairy industry worldwide. This study focuses on obtaining single-chain fragment variables (scFvs) against the virulence factors of <i>S. aureus</i> and...

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Autores principales: Lei Zhang, Xin Ye, Yan Zhang, Fengqing Wang, Fanqing Zhang, Yan Jia, Dangjin Wu, Kalbinur Tohti, Manling Cheng, Jianguo Zhu
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/6a6da6ed37cc49b687b4bd52087df297
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spelling oai:doaj.org-article:6a6da6ed37cc49b687b4bd52087df2972021-11-25T19:11:05ZAnti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo10.3390/vaccines91113002076-393Xhttps://doaj.org/article/6a6da6ed37cc49b687b4bd52087df2972021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1300https://doaj.org/toc/2076-393X<i>Staphylococcus aureus</i> is a causative agent of bovine mastitis, capable of causing significant economic losses to the dairy industry worldwide. This study focuses on obtaining single-chain fragment variables (scFvs) against the virulence factors of <i>S. aureus</i> and evaluates the protective effect of scFvs on bovine mammary epithelial (MAC-T) cells and mice mammary gland tissues infected by <i>S. aureus</i>. After five rounds of bio-panning, four scFvs targeting four virulence factors of <i>S. aureus</i> were obtained. The complementarity-determining regions (CDRs) of these scFvs exhibited significant diversities, especially CDR3 of the VH domain. In vitro, each of scFvs was capable of inhibiting <i>S. aureus</i> growth and reducing the damage of MAC-T cells infected by <i>S. aureus</i>. Preincubation of MAC-T cells with scFvs could significantly attenuate the effect of apoptosis and necrosis compared with the negative control group. In vivo, the qPCR and ELISA results demonstrated that scFvs reduced the transcription and expression of Tumor Necrosis Factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, and IL-18. Histopathology and myeloperoxidase (MPO) results showed that scFvs ameliorated the histopathological damages and reduced the inflammatory cells infiltration. The overall results demonstrated the positive anti-inflammatory effect of scFvs, revealing the potential role of scFvs in the prevention and treatment of <i>S. aureus</i> infections.Lei ZhangXin YeYan ZhangFengqing WangFanqing ZhangYan JiaDangjin WuKalbinur TohtiManling ChengJianguo ZhuMDPI AGarticlebovine mastitis<i>Staphylococcus aureus</i> (<i>S. aureus</i>)single-chain fragment variable (scFv)bovine mammary epithelial (MAC-T) cellscytotoxicityanti-inflammatoryMedicineRENVaccines, Vol 9, Iss 1300, p 1300 (2021)
institution DOAJ
collection DOAJ
language EN
topic bovine mastitis
<i>Staphylococcus aureus</i> (<i>S. aureus</i>)
single-chain fragment variable (scFv)
bovine mammary epithelial (MAC-T) cells
cytotoxicity
anti-inflammatory
Medicine
R
spellingShingle bovine mastitis
<i>Staphylococcus aureus</i> (<i>S. aureus</i>)
single-chain fragment variable (scFv)
bovine mammary epithelial (MAC-T) cells
cytotoxicity
anti-inflammatory
Medicine
R
Lei Zhang
Xin Ye
Yan Zhang
Fengqing Wang
Fanqing Zhang
Yan Jia
Dangjin Wu
Kalbinur Tohti
Manling Cheng
Jianguo Zhu
Anti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo
description <i>Staphylococcus aureus</i> is a causative agent of bovine mastitis, capable of causing significant economic losses to the dairy industry worldwide. This study focuses on obtaining single-chain fragment variables (scFvs) against the virulence factors of <i>S. aureus</i> and evaluates the protective effect of scFvs on bovine mammary epithelial (MAC-T) cells and mice mammary gland tissues infected by <i>S. aureus</i>. After five rounds of bio-panning, four scFvs targeting four virulence factors of <i>S. aureus</i> were obtained. The complementarity-determining regions (CDRs) of these scFvs exhibited significant diversities, especially CDR3 of the VH domain. In vitro, each of scFvs was capable of inhibiting <i>S. aureus</i> growth and reducing the damage of MAC-T cells infected by <i>S. aureus</i>. Preincubation of MAC-T cells with scFvs could significantly attenuate the effect of apoptosis and necrosis compared with the negative control group. In vivo, the qPCR and ELISA results demonstrated that scFvs reduced the transcription and expression of Tumor Necrosis Factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, and IL-18. Histopathology and myeloperoxidase (MPO) results showed that scFvs ameliorated the histopathological damages and reduced the inflammatory cells infiltration. The overall results demonstrated the positive anti-inflammatory effect of scFvs, revealing the potential role of scFvs in the prevention and treatment of <i>S. aureus</i> infections.
format article
author Lei Zhang
Xin Ye
Yan Zhang
Fengqing Wang
Fanqing Zhang
Yan Jia
Dangjin Wu
Kalbinur Tohti
Manling Cheng
Jianguo Zhu
author_facet Lei Zhang
Xin Ye
Yan Zhang
Fengqing Wang
Fanqing Zhang
Yan Jia
Dangjin Wu
Kalbinur Tohti
Manling Cheng
Jianguo Zhu
author_sort Lei Zhang
title Anti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo
title_short Anti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo
title_full Anti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo
title_fullStr Anti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo
title_full_unstemmed Anti-<i>Staphylococcus aureus</i> Single-Chain Fragment Variables Play a Protective Anti-Inflammatory Role In Vitro and In Vivo
title_sort anti-<i>staphylococcus aureus</i> single-chain fragment variables play a protective anti-inflammatory role in vitro and in vivo
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/6a6da6ed37cc49b687b4bd52087df297
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