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Development of nanobodies specific to clumping factors A of Staphylococcus aureus by yeast surface display.
Mei, Meng; Lu, Mengqing; Li, Shiqi; Ren, Xinyi; Xing, Banbin; Hu, Yang; Wu, Yuqi; Chen, Huan; Wang, Longhao; Yi, Li; Ming, Ke; Wei, Zigong.
Afiliación
  • Mei M; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China; Hubei Jiangxia Laboratory, Wuhan, Hubei, China.
  • Lu M; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Li S; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Ren X; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Xing B; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Hu Y; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Wu Y; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Chen H; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Wang L; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Yi L; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
  • Ming K; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China; Hubei Jiangxia Laboratory, Wuhan, Hubei, China.
  • Wei Z; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China; Hubei Jiangxia Laboratory, Wuhan, Hubei, China; Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research
Int J Biol Macromol ; 259(Pt 2): 129208, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38185298
ABSTRACT
The Staphylococcus aureus clumping factor A (ClfA) is a fibrinogen (Fg) binding protein that plays an important role in the clumping of S. aureus in blood plasma. The current anti-infective approaches targeting ClfA are mainly based on monoclonal antibodies but showed less impressive efficacy for clinical applications. Nanobodies offer advantages in enhanced tissue penetration and a propensity to bind small epitopes. However, there is no report on generating specific nanobodies for ClfA. Here, we constructed a synthetic nanobody library based on yeast surface display to isolate nanobodies against the Fg binding domain ClfA221-550. We firstly obtained a primary nanobody directed to ClfA221-550, and then employed error-prone mutagenesis to enhance its binding affinity. Finally, 18 variants were isolated with high affinities (EC50, 1.1 ± 0.1 nM to 4.8 ± 0.3 nM), in which CNb1 presented the highest inhibition efficiency in the adhesion of S. aureus to fibrinogen. Moreover, structural simulation analysis indicated that the epitope for CNb1 partially overlapped with the binding sites for fibrinogen, thus inhibiting ClfA binding to Fg. Overall, these results indicated that the specific nanobodies generated here could prevent the adhesion of S. aureus to fibrinogen, suggesting their potential capacities in the control of S. aureus infections.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / Anticuerpos de Dominio Único Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / Anticuerpos de Dominio Único Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos