posted on 2024-03-08, 13:04authored byLiang Fang, Simian Cai, Patrick McMullen, Yi-Chen Hsu, Michelle Yi Qin Chen, Shaoyi Jiang
Living microbial therapies have been proposed as a course
of action
for a variety of diseases. However, problematic interactions between
the host immune system and the microbial organism present significant
clinical concerns. Previously, we developed a genetically encoded
superhydrophilic zwitterionic peptide, termed EKP, to mimic low-immunogenic
zwitterionic materials, which have been used for the chemical modification
of biologics such as protein and nucleic acid drugs to increase their
in vivo circulation time and reduce their immunogenicity. Herein,
we demonstrate the protective effects of the EKP polypeptide genetically
cloaking the surface of Saccharomyces cerevisiae as
a model microbe in both in vitro and in vivo systems. First, we show
that EKP peptide cloaking suppresses the interactions between yeast
cells and their specific antibodies, thereby illustrating its cloaking
behavior. Then, we examine the in vitro interactions between EKP peptide
surface cloaked yeast cells and murine macrophage cells, which exhibit
phagocytotic behavior in the presence of foreign microbes. Our results
indicate that EKP cloaking suppresses macrophage interactions and
thus reduces phagocytosis. Furthermore, EKP cloaked yeast cells demonstrate
a prolonged circulation time in mice in vivo.