Peptide selection via phage display to inhibit Leishmania-macrophage interactions
IntroductionLeishmaniasis comprises a complex group of diseases caused by protozoan parasites from the Leishmania genus, presenting a significant threat to human health. Infection starts by the release into the skin of metacyclic promastigote (MP) form of the parasite by an infected sand fly. Soon a...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1362252/full |
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| author | Juliane Buzzon Meneghesso Verga Márcia A. S. Graminha Marcelo Jacobs-Lorena Sung-Jae Cha |
| author_facet | Juliane Buzzon Meneghesso Verga Márcia A. S. Graminha Marcelo Jacobs-Lorena Sung-Jae Cha |
| author_sort | Juliane Buzzon Meneghesso Verga |
| collection | DOAJ |
| description | IntroductionLeishmaniasis comprises a complex group of diseases caused by protozoan parasites from the Leishmania genus, presenting a significant threat to human health. Infection starts by the release into the skin of metacyclic promastigote (MP) form of the parasite by an infected sand fly. Soon after their release, the MPs enter a phagocytic host cell. This study focuses on finding peptides that can inhibit MP-phagocytic host cell interaction.MethodsWe 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.ResultsThe 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%.ConclusionWe 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. |
| first_indexed | 2024-03-07T21:25:54Z |
| format | Article |
| id | doaj.art-78acb6cea7c8431aa3719f91dcfa4eb7 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-07T21:25:54Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-78acb6cea7c8431aa3719f91dcfa4eb72024-02-27T04:49:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-02-011510.3389/fmicb.2024.13622521362252Peptide selection via phage display to inhibit Leishmania-macrophage interactionsJuliane Buzzon Meneghesso Verga0Márcia A. S. Graminha1Marcelo Jacobs-Lorena2Sung-Jae Cha3Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, BrazilMolecular Microbiology & Immunology, Johns Hopkins Malaria Research Institute, Johns Hopkins School of Public Health, Baltimore, MD, United StatesDepartment of Medical Sciences, Mercer University School of Medicine, Macon, GA, United StatesIntroductionLeishmaniasis comprises a complex group of diseases caused by protozoan parasites from the Leishmania genus, presenting a significant threat to human health. Infection starts by the release into the skin of metacyclic promastigote (MP) form of the parasite by an infected sand fly. Soon after their release, the MPs enter a phagocytic host cell. This study focuses on finding peptides that can inhibit MP-phagocytic host cell interaction.MethodsWe 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.ResultsThe 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%.ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1362252/fullphage display 12-mer peptide libraryLeishmania-macrophage interactionligand-receptor interactionmetacyclic promastigotevisceral leishmaniasis |
| spellingShingle | Juliane Buzzon Meneghesso Verga Márcia A. S. Graminha Marcelo Jacobs-Lorena Sung-Jae Cha Peptide selection via phage display to inhibit Leishmania-macrophage interactions Frontiers in Microbiology phage display 12-mer peptide library Leishmania-macrophage interaction ligand-receptor interaction metacyclic promastigote visceral leishmaniasis |
| title | Peptide selection via phage display to inhibit Leishmania-macrophage interactions |
| title_full | Peptide selection via phage display to inhibit Leishmania-macrophage interactions |
| title_fullStr | Peptide selection via phage display to inhibit Leishmania-macrophage interactions |
| title_full_unstemmed | Peptide selection via phage display to inhibit Leishmania-macrophage interactions |
| title_short | Peptide selection via phage display to inhibit Leishmania-macrophage interactions |
| title_sort | peptide selection via phage display to inhibit leishmania macrophage interactions |
| topic | phage display 12-mer peptide library Leishmania-macrophage interaction ligand-receptor interaction metacyclic promastigote visceral leishmaniasis |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1362252/full |
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