Optimized Silica-Binding Peptide-Mediated Delivery of Bactericidal Lysin Efficiently Prevents Staphylococcus aureus from Adhering to Device Surfaces.

Wan Yang,Hongping Wei,Vijay Singh Gondil,Hang Yang,Dehua Luo,Jin He

doi:10.3390/ijms222212544

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.

Highlights

Medical devices play a pivotal role in the management of healthcare-associated patients in modern medicine
Considering the epidemiology and threats of staphylococci-primed devicerelated infections (DRIs) in model healthcare settings, we further explored the antistaphylococcal capacity of surface-immobilized ClyF by using solid surface directed silica-binding peptide (SiBP)
Three peptides varying in charge and length, i.e., a 12-residue peptide SiBP1 (MSPHPHPRHHHT; Z = +1) [30], a 19-residue peptide SiBP2 (SSKKSGSYSGSKGSKRRIL; Z = +6) [31], and another 12-residue peptide SiBP3 (HPPMNASHPHMH; Z = 0) [32], were selected fusing to the C-terminal of ClyF lysin (Figure 1)

Summary

Introduction

Medical devices play a pivotal role in the management of healthcare-associated patients in modern medicine. Indwelling urinary and central venous catheters are the most frequently employed invasive devices, which have revolutionized medical treatment, especially post-operative care [1]. These catheters remain continuously interacting with body fluids for a long duration, which is critical for the success of these implants [2]. Long-term catheterization favors microbial colonization and dissemination, leading to the failure of implant and further increasing the treatment cost and the severity of ailment [3]. A 3–6% per day increased risk of bacterial colonization has been estimated in urinary catheterization and 7–10 days of catheterization may result in catheterassociated infections in 50% of the hospitalized patients [4,5]. Bacterial colonization on surface of central venous catheters presents more serious complications as compared to urinary catheters, as relatively small number of colonized bacteria can successfully estab-

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Discussion

Conclusion