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Optimized Silica-Binding Peptide-Mediated Delivery of Bactericidal Lysin Efficiently Prevents Staphylococcus aureus from Adhering to Device Surfaces
Authors:Wan Yang  Vijay Singh Gondil  Dehua Luo  Jin He  Hongping Wei  Hang Yang
Affiliation:1.State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; (W.Y.); (D.L.); (J.H.);2.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; (V.S.G.); (H.W.);3.University of Chinese Academy of Sciences, Beijing 100049, China
Abstract:
Staphylococcal-associated device-related infections (DRIs) represent a significant clinical challenge causing major medical and economic sequelae. Bacterial colonization, proliferation, and biofilm formation after adherence to surfaces of the indwelling device are probably the primary cause of DRIs. To address this issue, we incorporated constructs of silica-binding peptide (SiBP) with ClyF, an anti-staphylococcal lysin, into functionalized coatings to impart bactericidal activity against planktonic and sessile Staphylococcus aureus. An optimized construct, SiBP1-ClyF, exhibited improved thermostability and staphylolytic activity compared to its parental lysin ClyF. SiBP1-ClyF-functionalized coatings were efficient in killing MRSA strain N315 (>99.999% within 1 h) and preventing the growth of static and dynamic S. aureus biofilms on various surfaces, including siliconized glass, silicone-coated latex catheter, and silicone catheter. Additionally, SiBP1-ClyF-immobilized surfaces supported normal attachment and growth of mammalian cells. Although the recycling potential and long-term stability of lysin-immobilized surfaces are still affected by the fragility of biological protein molecules, the present study provides a generic strategy for efficient delivery of bactericidal lysin to solid surfaces, which serves as a new approach to prevent the growth of antibiotic-resistant microorganisms on surfaces in hospital settings and could be adapted for other target pathogens as well.
Keywords:lysin   Staphylococcus aureus   silica-binding peptide   antimicrobial agents immobilization   surface functionalization   antimicrobial agents   biofilm
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