Heme crystallization in a Chagas disease vector acts as a redox-protective mechanism to allow insect reproduction and parasite infection
Heme crystallization as hemozoin represents the dominant mechanism of heme disposal in blood feeding triatomine insect vectors of the Chagas disease. The absence of drugs or vaccine for the Chagas disease causative agent, the parasite Trypanosoma cruzi, makes the control of vector population the bes...
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creator | Ferreira, Caroline M Stiebler, Renata Saraiva, Francis M Lechuga, Guilherme C Walter-Nuno, Ana Beatriz Bourguignon, Saulo C Gonzalez, Marcelo S Azambuja, Patrícia Gandara, Ana Caroline P Menna-Barreto, Rubem F S Paiva-Silva, Gabriela O Paes, Marcia C Oliveira, Marcus F |
description | Heme crystallization as hemozoin represents the dominant mechanism of heme disposal in blood feeding triatomine insect vectors of the Chagas disease. The absence of drugs or vaccine for the Chagas disease causative agent, the parasite Trypanosoma cruzi, makes the control of vector population the best available strategy to limit disease spread. Although heme and redox homeostasis regulation is critical for both triatomine insects and T. cruzi, the physiological relevance of hemozoin for these organisms remains unknown. Here, we demonstrate that selective blockage of heme crystallization in vivo by the antimalarial drug quinidine, caused systemic heme overload and redox imbalance in distinct insect tissues, assessed by spectrophotometry and fluorescence microscopy. Quinidine treatment activated compensatory defensive heme-scavenging mechanisms to cope with excessive heme, as revealed by biochemical hemolymph analyses, and fat body gene expression. Importantly, egg production, oviposition, and total T. cruzi parasite counts in R. prolixus were significantly reduced by quinidine treatment. These effects were reverted by oral supplementation with the major insect antioxidant urate. Altogether, these data underscore the importance of heme crystallization as the main redox regulator for triatomine vectors, indicating the dual role of hemozoin as a protective mechanism to allow insect fertility, and T. cruzi life-cycle. Thus, targeting heme crystallization in insect vectors represents an innovative way for Chagas disease control, by reducing simultaneously triatomine reproduction and T. cruzi transmission. |
doi_str_mv | 10.1371/journal.pntd.0006661 |
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The absence of drugs or vaccine for the Chagas disease causative agent, the parasite Trypanosoma cruzi, makes the control of vector population the best available strategy to limit disease spread. Although heme and redox homeostasis regulation is critical for both triatomine insects and T. cruzi, the physiological relevance of hemozoin for these organisms remains unknown. Here, we demonstrate that selective blockage of heme crystallization in vivo by the antimalarial drug quinidine, caused systemic heme overload and redox imbalance in distinct insect tissues, assessed by spectrophotometry and fluorescence microscopy. Quinidine treatment activated compensatory defensive heme-scavenging mechanisms to cope with excessive heme, as revealed by biochemical hemolymph analyses, and fat body gene expression. Importantly, egg production, oviposition, and total T. cruzi parasite counts in R. prolixus were significantly reduced by quinidine treatment. These effects were reverted by oral supplementation with the major insect antioxidant urate. Altogether, these data underscore the importance of heme crystallization as the main redox regulator for triatomine vectors, indicating the dual role of hemozoin as a protective mechanism to allow insect fertility, and T. cruzi life-cycle. Thus, targeting heme crystallization in insect vectors represents an innovative way for Chagas disease control, by reducing simultaneously triatomine reproduction and T. cruzi transmission.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0006661</identifier><identifier>PMID: 30036366</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antioxidants ; Biology and Life Sciences ; Blockage ; Chagas disease ; Crystallization ; Dietary supplements ; Disease control ; Disease spread ; Disease transmission ; Diseases ; Drug therapy ; Egg production ; Fat body ; Fertility ; Fluorescence ; Fluorescence microscopy ; Gene expression ; Genetic aspects ; Heme ; Hemolymph ; Hemozoin ; Homeostasis ; Insects ; Kinases ; Medicine and Health Sciences ; Molecular biology ; Oviposition ; Oxidative stress ; Oxidoreductions ; Parasites ; Physical Sciences ; Physiological aspects ; Protozoa ; Quinidine ; Reproduction ; Spectrophotometry ; Tissue ; Transmission ; Tropical diseases ; Trypanosoma cruzi ; Uric acid ; Vaccines ; Vector-borne diseases ; Vectors</subject><ispartof>PLoS neglected tropical diseases, 2018-07, Vol.12 (7), p.e0006661-e0006661</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The absence of drugs or vaccine for the Chagas disease causative agent, the parasite Trypanosoma cruzi, makes the control of vector population the best available strategy to limit disease spread. Although heme and redox homeostasis regulation is critical for both triatomine insects and T. cruzi, the physiological relevance of hemozoin for these organisms remains unknown. Here, we demonstrate that selective blockage of heme crystallization in vivo by the antimalarial drug quinidine, caused systemic heme overload and redox imbalance in distinct insect tissues, assessed by spectrophotometry and fluorescence microscopy. Quinidine treatment activated compensatory defensive heme-scavenging mechanisms to cope with excessive heme, as revealed by biochemical hemolymph analyses, and fat body gene expression. Importantly, egg production, oviposition, and total T. cruzi parasite counts in R. prolixus were significantly reduced by quinidine treatment. These effects were reverted by oral supplementation with the major insect antioxidant urate. Altogether, these data underscore the importance of heme crystallization as the main redox regulator for triatomine vectors, indicating the dual role of hemozoin as a protective mechanism to allow insect fertility, and T. cruzi life-cycle. Thus, targeting heme crystallization in insect vectors represents an innovative way for Chagas disease control, by reducing simultaneously triatomine reproduction and T. cruzi transmission.</description><subject>Antioxidants</subject><subject>Biology and Life Sciences</subject><subject>Blockage</subject><subject>Chagas disease</subject><subject>Crystallization</subject><subject>Dietary supplements</subject><subject>Disease control</subject><subject>Disease spread</subject><subject>Disease transmission</subject><subject>Diseases</subject><subject>Drug therapy</subject><subject>Egg production</subject><subject>Fat body</subject><subject>Fertility</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Heme</subject><subject>Hemolymph</subject><subject>Hemozoin</subject><subject>Homeostasis</subject><subject>Insects</subject><subject>Kinases</subject><subject>Medicine and Health 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crystallization in a Chagas disease vector acts as a redox-protective mechanism to allow insect reproduction and parasite infection</title><author>Ferreira, Caroline M ; Stiebler, Renata ; Saraiva, Francis M ; Lechuga, Guilherme C ; Walter-Nuno, Ana Beatriz ; Bourguignon, Saulo C ; Gonzalez, Marcelo S ; Azambuja, Patrícia ; Gandara, Ana Caroline P ; Menna-Barreto, Rubem F S ; Paiva-Silva, Gabriela O ; Paes, Marcia C ; Oliveira, Marcus F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-26bb2a5d07459b291f0e808d52e6328c89bdd85526069737ca858d1943d28d683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Antioxidants</topic><topic>Biology and Life Sciences</topic><topic>Blockage</topic><topic>Chagas disease</topic><topic>Crystallization</topic><topic>Dietary supplements</topic><topic>Disease control</topic><topic>Disease spread</topic><topic>Disease transmission</topic><topic>Diseases</topic><topic>Drug therapy</topic><topic>Egg production</topic><topic>Fat body</topic><topic>Fertility</topic><topic>Fluorescence</topic><topic>Fluorescence microscopy</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Heme</topic><topic>Hemolymph</topic><topic>Hemozoin</topic><topic>Homeostasis</topic><topic>Insects</topic><topic>Kinases</topic><topic>Medicine and Health Sciences</topic><topic>Molecular biology</topic><topic>Oviposition</topic><topic>Oxidative stress</topic><topic>Oxidoreductions</topic><topic>Parasites</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Protozoa</topic><topic>Quinidine</topic><topic>Reproduction</topic><topic>Spectrophotometry</topic><topic>Tissue</topic><topic>Transmission</topic><topic>Tropical diseases</topic><topic>Trypanosoma cruzi</topic><topic>Uric acid</topic><topic>Vaccines</topic><topic>Vector-borne 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S</au><au>Azambuja, Patrícia</au><au>Gandara, Ana Caroline P</au><au>Menna-Barreto, Rubem F S</au><au>Paiva-Silva, Gabriela O</au><au>Paes, Marcia C</au><au>Oliveira, Marcus F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heme crystallization in a Chagas disease vector acts as a redox-protective mechanism to allow insect reproduction and parasite infection</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2018-07-23</date><risdate>2018</risdate><volume>12</volume><issue>7</issue><spage>e0006661</spage><epage>e0006661</epage><pages>e0006661-e0006661</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Heme crystallization as hemozoin represents the dominant mechanism of heme disposal in blood feeding triatomine insect vectors of the Chagas disease. The absence of drugs or vaccine for the Chagas disease causative agent, the parasite Trypanosoma cruzi, makes the control of vector population the best available strategy to limit disease spread. Although heme and redox homeostasis regulation is critical for both triatomine insects and T. cruzi, the physiological relevance of hemozoin for these organisms remains unknown. Here, we demonstrate that selective blockage of heme crystallization in vivo by the antimalarial drug quinidine, caused systemic heme overload and redox imbalance in distinct insect tissues, assessed by spectrophotometry and fluorescence microscopy. Quinidine treatment activated compensatory defensive heme-scavenging mechanisms to cope with excessive heme, as revealed by biochemical hemolymph analyses, and fat body gene expression. Importantly, egg production, oviposition, and total T. cruzi parasite counts in R. prolixus were significantly reduced by quinidine treatment. These effects were reverted by oral supplementation with the major insect antioxidant urate. Altogether, these data underscore the importance of heme crystallization as the main redox regulator for triatomine vectors, indicating the dual role of hemozoin as a protective mechanism to allow insect fertility, and T. cruzi life-cycle. Thus, targeting heme crystallization in insect vectors represents an innovative way for Chagas disease control, by reducing simultaneously triatomine reproduction and T. cruzi transmission.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30036366</pmid><doi>10.1371/journal.pntd.0006661</doi><orcidid>https://orcid.org/0000-0003-3194-4453</orcidid><orcidid>https://orcid.org/0000-0002-6744-3549</orcidid><orcidid>https://orcid.org/0000-0001-8751-7886</orcidid><orcidid>https://orcid.org/0000-0003-4538-3802</orcidid><orcidid>https://orcid.org/0000-0002-9890-8425</orcidid><orcidid>https://orcid.org/0000-0003-3835-5416</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antioxidants Biology and Life Sciences Blockage Chagas disease Crystallization Dietary supplements Disease control Disease spread Disease transmission Diseases Drug therapy Egg production Fat body Fertility Fluorescence Fluorescence microscopy Gene expression Genetic aspects Heme Hemolymph Hemozoin Homeostasis Insects Kinases Medicine and Health Sciences Molecular biology Oviposition Oxidative stress Oxidoreductions Parasites Physical Sciences Physiological aspects Protozoa Quinidine Reproduction Spectrophotometry Tissue Transmission Tropical diseases Trypanosoma cruzi Uric acid Vaccines Vector-borne diseases Vectors |
title | Heme crystallization in a Chagas disease vector acts as a redox-protective mechanism to allow insect reproduction and parasite infection |
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