Peptide selection via phage display to inhibit Leishmania-macrophage interactions

通过噬菌体展示选择肽来抑制利什曼原虫-巨噬细胞相互作用

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作者:Juliane Buzzon Meneghesso Verga, Márcia A S Graminha, Marcelo Jacobs-Lorena, Sung-Jae Cha

Conclusion

We identified one peptide that specifically inhibits L. amazonensis MP infection of host cells and another that inhibits both, L. amazonensis and L. infantum, MP infection. Our findings suggest a promising path for the development of new treatments and prevention of leishmaniasis.

Methods

We used a phage display library to screen for peptides that bind to the surface of L. amazonensis (causative agent for cutaneous leishmaniasis) and L. infantum (causative agent for cutaneous and visceral leishmaniasis) MPs. Candidate peptide binding to the MP surface and inhibition of parasite-host cell interaction were tested in vitro. Peptide Inhibition of visceral leishmaniasis development was assessed in BALB/c mice.

Results

The selected L. amazonensis binding peptide (La1) and the L. infantum binding peptide (Li1) inhibited 44% of parasite internalization into THP-1 macrophage-like cells in vitro. While inhibition of internalization by La1 was specific to L. amazonensis, Li1 was effective in inhibiting internalization of both parasite species. Importantly, Li1 inhibited L. infantum spleen and liver infection of BALB/c mice by 84%.

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