Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi.
<h4>Background</h4>During its developmental cycle within the sand fly vector, Leishmania must survive an early proteolytic attack, escape the peritrophic matrix, and then adhere to the midgut epithelia in order to prevent excretion with remnants of the blood meal. These three steps are c...
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Public Library of Science (PLoS)
2010-11-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0000901&type=printable |
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| author | Iliano V Coutinho-Abreu Narinder K Sharma Maricela Robles-Murguia Marcelo Ramalho-Ortigao |
| author_facet | Iliano V Coutinho-Abreu Narinder K Sharma Maricela Robles-Murguia Marcelo Ramalho-Ortigao |
| author_sort | Iliano V Coutinho-Abreu |
| collection | DOAJ |
| description | <h4>Background</h4>During its developmental cycle within the sand fly vector, Leishmania must survive an early proteolytic attack, escape the peritrophic matrix, and then adhere to the midgut epithelia in order to prevent excretion with remnants of the blood meal. These three steps are critical for the establishment of an infection within the vector and are linked to interactions controlling species-specific vector competence. PpChit1 is a midgut-specific chitinase from Phlebotomus papatasi presumably involved in maturation and degradation of the peritrophic matrix. Sand fly midgut chitinases, such as PpChit1, whether acting independently or in a synergistic manner with Leishmania-secreted chitinase, possibly play a role in the Leishmania escape from the endoperitrophic space. Thus, we predicted that silencing of sand fly chitinase will lead to reduction or elimination of Leishmania within the gut of the sand fly vector.<h4>Methodology/principal findings</h4>We used injection of dsRNA to induce knock down of PpChit1 transcripts (dsPpChit1) and assessed the effect on protein levels post blood meal (PBM) and on Leishmania major development within P. papatasi. Injection of dsPpChit1 led to a significant reduction of PpChit1 transcripts from 24 hours to 96 hours PBM. More importantly, dsPpChit1 led to a significant reduction in protein levels and in the number of Le. major present in the midgut of infected P. papatasi following a infective blood meal.<h4>Conclusion/significance</h4>Our data supports targeting PpChit1 as a potential transmission blocking vaccine candidate against leishmaniasis. |
| format | Article |
| id | doaj-art-52a17006467241c3992ca55fa9fdc96e |
| institution | DOAJ |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2010-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-52a17006467241c3992ca55fa9fdc96e2025-08-20T03:07:41ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352010-11-01411e90110.1371/journal.pntd.0000901Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi.Iliano V Coutinho-AbreuNarinder K SharmaMaricela Robles-MurguiaMarcelo Ramalho-Ortigao<h4>Background</h4>During its developmental cycle within the sand fly vector, Leishmania must survive an early proteolytic attack, escape the peritrophic matrix, and then adhere to the midgut epithelia in order to prevent excretion with remnants of the blood meal. These three steps are critical for the establishment of an infection within the vector and are linked to interactions controlling species-specific vector competence. PpChit1 is a midgut-specific chitinase from Phlebotomus papatasi presumably involved in maturation and degradation of the peritrophic matrix. Sand fly midgut chitinases, such as PpChit1, whether acting independently or in a synergistic manner with Leishmania-secreted chitinase, possibly play a role in the Leishmania escape from the endoperitrophic space. Thus, we predicted that silencing of sand fly chitinase will lead to reduction or elimination of Leishmania within the gut of the sand fly vector.<h4>Methodology/principal findings</h4>We used injection of dsRNA to induce knock down of PpChit1 transcripts (dsPpChit1) and assessed the effect on protein levels post blood meal (PBM) and on Leishmania major development within P. papatasi. Injection of dsPpChit1 led to a significant reduction of PpChit1 transcripts from 24 hours to 96 hours PBM. More importantly, dsPpChit1 led to a significant reduction in protein levels and in the number of Le. major present in the midgut of infected P. papatasi following a infective blood meal.<h4>Conclusion/significance</h4>Our data supports targeting PpChit1 as a potential transmission blocking vaccine candidate against leishmaniasis.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0000901&type=printable |
| spellingShingle | Iliano V Coutinho-Abreu Narinder K Sharma Maricela Robles-Murguia Marcelo Ramalho-Ortigao Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi. PLoS Neglected Tropical Diseases |
| title | Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi. |
| title_full | Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi. |
| title_fullStr | Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi. |
| title_full_unstemmed | Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi. |
| title_short | Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi. |
| title_sort | targeting the midgut secreted ppchit1 reduces leishmania major development in its natural vector the sand fly phlebotomus papatasi |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0000901&type=printable |
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