Targeting the midgut secreted PpChit1 reduces Leishmania major development in its natural vector, the sand fly Phlebotomus papatasi.

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 o...

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Main Authors: Iliano V Coutinho-Abreu, Narinder K Sharma, Maricela Robles-Murguia, Marcelo Ramalho-Ortigao
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-11-01
Series:PLoS Neglected Tropical Diseases
Online Access:http://europepmc.org/articles/PMC2994919?pdf=render
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spelling doaj-52a17006467241c3992ca55fa9fdc96e2020-11-24T21:58:52ZengPublic 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-OrtigaoDuring 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.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.Our data supports targeting PpChit1 as a potential transmission blocking vaccine candidate against leishmaniasis.http://europepmc.org/articles/PMC2994919?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Iliano V Coutinho-Abreu
Narinder K Sharma
Maricela Robles-Murguia
Marcelo Ramalho-Ortigao
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
author_facet Iliano V Coutinho-Abreu
Narinder K Sharma
Maricela Robles-Murguia
Marcelo Ramalho-Ortigao
author_sort Iliano V Coutinho-Abreu
title 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_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_sort targeting the midgut secreted ppchit1 reduces leishmania major development in its natural vector, the sand fly phlebotomus papatasi.
publisher Public Library of Science (PLoS)
series PLoS Neglected Tropical Diseases
issn 1935-2727
1935-2735
publishDate 2010-11-01
description 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.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.Our data supports targeting PpChit1 as a potential transmission blocking vaccine candidate against leishmaniasis.
url http://europepmc.org/articles/PMC2994919?pdf=render
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