Abstract
Staphylococcus aureus (S. aureus) is the most common cause of hospital and community-acquired infections. The current clinical treatment is limited by the emergence of drug-resistant strains. We previously developed a chimeric ClyC that effectively inhibited S. aureus strains. Nonetheless, an efficient delivery system to provide sustained release of ClyC to infected site is needed. Thus, we engineered a chimeric ClyC loaded alginate hydrogel (ClyC-AH) to improve the therapeutic outcomes against S. aureus. ClyC-AH retained the stability and activity of ClyC while providing a sustained release of ClyC and a continuous antibacterial effect against S. aureus. Compared to ClyC alone, the use of ClyC-AH was relatively safe, as there was no significant cytotoxicity to BHK-21 cells at a ClyC concentration≤250 μg/ml. Furthermore, in a S. aureus infected mouse model of osteomyelitis, ClyC-AH reduced bacterial burden in the femur and surrounding tissues, with a reduction of 2 log10 (CFU/ml) in viable bacterial number. Based on these results, hydrogel-delivered chimeric lysin ClyC provides a promising future in the S.aureus targeting therapy.
Highlights
Staphylococcus aureus (S. aureus) is a Gram-positive pathogen that primarily colonizes on the nostrils, skin, and mucosal membranes of human (Lowy, 1998; Becker and Bubeck Wardenburg, 2015)
Chitosan nanoparticles loaded with the Cpl-1 pneumococcal endolysin showed low cytotoxicity to lung epithelial cell lines and reduced bacterial colonization in the lungs of mice (Gondil et al, 2020a)
LysRODI encapsulated in pH-sensitive liposomes reduced S. aureus counts by 2log units upon incubation at pH 5 (Portilla et al, 2020)
Summary
Staphylococcus aureus (S. aureus) is a Gram-positive pathogen that primarily colonizes on the nostrils, skin, and mucosal membranes of human (Lowy, 1998; Becker and Bubeck Wardenburg, 2015). Alginate hydrogels are widely used in wound dressing and bone and cardiac tissue engineering due to their biocompatibility, low cytotoxicity, low immunogenicity, and biodegradability (Ruvinov and Cohen, 2016; Varaprasad et al, 2020). They are ideal materials for the delivery of protein drugs because they can be prepared under mild pH and temperature conditions (Lee and Mooney, 2012). Antibacterial agents have been encapsulated in alginate hydrogel in order to target specific pathogens and reduce infections. The change of bacteria colony forming unit (CFU) was tested to demonstrate the therapeutic potential of the ClyC-AH
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