Effects of miltefosine on the proliferation, ultrastructure, and phospholipid composition of Angomonas deanei, a trypanosomatid protozoan that harbors a symbiotic bacterium

Abstract Some trypanosomatids, such as Angomonas deanei formerly named as Crithidia deanei, present an obligatory intracellular bacterium, which maintains a mutualistic relationship with the host. Phosphatidylcholine (PC) is the major phospholipid in eukaryotes and an essential component of cell mem...

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Veröffentlicht in:FEMS microbiology letters 2012-08, Vol.333 (2), p.129-137
Hauptverfasser: de Freitas-Junior, Paulo R.G., Catta-Preta, Carolina M.C., Andrade, Iamara da Silva, Cavalcanti, Danielle P., de Souza, Wanderley, Einicker-Lamas, Marcelo, Motta, Maria Cristina M.
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container_end_page 137
container_issue 2
container_start_page 129
container_title FEMS microbiology letters
container_volume 333
creator de Freitas-Junior, Paulo R.G.
Catta-Preta, Carolina M.C.
Andrade, Iamara da Silva
Cavalcanti, Danielle P.
de Souza, Wanderley
Einicker-Lamas, Marcelo
Motta, Maria Cristina M.
description Abstract Some trypanosomatids, such as Angomonas deanei formerly named as Crithidia deanei, present an obligatory intracellular bacterium, which maintains a mutualistic relationship with the host. Phosphatidylcholine (PC) is the major phospholipid in eukaryotes and an essential component of cell membranes playing structural, biochemical, and physiological roles. However, in prokaryotes, PC is present only in those species closely associated with eukaryotes, either in symbiotic or pathogenic interactions. In trypanosomatids, the endosymbiont envelope is composed by a reduced cell wall and by two membrane units that lack sterols and present cardiolipin (CL) and PC as the major phospholipids. In this study, we tested the effects of miltefosine in A. deanei proliferation, as well as, on the ultrastrucuture and phospholipid composition considering that this drug inhibits the CTP-phosphocholine cytidyltransferase (CCT), a key enzyme in the PC biosynthesis. Besides the low effect of miltefosine in cellular proliferation, treated protozoa presented ultrastructural alterations such as plasma membrane shedding and blebbing, mitochondrial swelling, and convolutions of the endosymbiont envelope. The use of 32Pi as a tracer revealed that the production of PC, CL, and phosphatidylethanolamine decreased while phosphatidylinositol production remained stable. Mitochondrion and symbiont fractions obtained from protozoa treated with miltefosine also presented a decrease in phospholipid production, reinforcing the idea that an intensive metabolic exchange occurs between the host trypanosomatid and structures of symbiotic origin.
doi_str_mv 10.1111/j.1574-6968.2012.02607.x
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Phosphatidylcholine (PC) is the major phospholipid in eukaryotes and an essential component of cell membranes playing structural, biochemical, and physiological roles. However, in prokaryotes, PC is present only in those species closely associated with eukaryotes, either in symbiotic or pathogenic interactions. In trypanosomatids, the endosymbiont envelope is composed by a reduced cell wall and by two membrane units that lack sterols and present cardiolipin (CL) and PC as the major phospholipids. In this study, we tested the effects of miltefosine in A. deanei proliferation, as well as, on the ultrastrucuture and phospholipid composition considering that this drug inhibits the CTP-phosphocholine cytidyltransferase (CCT), a key enzyme in the PC biosynthesis. Besides the low effect of miltefosine in cellular proliferation, treated protozoa presented ultrastructural alterations such as plasma membrane shedding and blebbing, mitochondrial swelling, and convolutions of the endosymbiont envelope. The use of 32Pi as a tracer revealed that the production of PC, CL, and phosphatidylethanolamine decreased while phosphatidylinositol production remained stable. Mitochondrion and symbiont fractions obtained from protozoa treated with miltefosine also presented a decrease in phospholipid production, reinforcing the idea that an intensive metabolic exchange occurs between the host trypanosomatid and structures of symbiotic origin.</description><identifier>ISSN: 0378-1097</identifier><identifier>EISSN: 1574-6968</identifier><identifier>DOI: 10.1111/j.1574-6968.2012.02607.x</identifier><identifier>PMID: 22651853</identifier><identifier>CODEN: FMLED7</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Angomonas deanei ; Bacteria ; Bacteria - drug effects ; Bacteria - growth &amp; development ; Biological and medical sciences ; Biosynthesis ; Cardiolipin ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cell Membrane - ultrastructure ; Cell membranes ; Cell Wall - drug effects ; Cell Wall - metabolism ; Cell walls ; Choline-Phosphate Cytidylyltransferase - metabolism ; Composition ; Crithidia - drug effects ; Crithidia - metabolism ; Crithidia - microbiology ; Crithidia - ultrastructure ; endosymbiosis ; Eukaryotes ; Fundamental and applied biological sciences. Psychology ; Lecithin ; Microbiology ; Microscopy, Electron, Transmission ; Miltefosine ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - ultrastructure ; Phosphatidylcholine ; Phosphatidylcholines - biosynthesis ; Phosphatidylethanolamine ; Phosphatidylinositol ; Phosphocholine ; phospholipid biosynthesis ; Phospholipid composition ; Phospholipids ; Phosphorus Isotopes - metabolism ; Phosphorylcholine - analogs &amp; derivatives ; Phosphorylcholine - pharmacology ; Prokaryotes ; Protozoa ; Sterols ; Symbiosis ; trypanosomatid protozoa ; Ultrastructure</subject><ispartof>FEMS microbiology letters, 2012-08, Vol.333 (2), p.129-137</ispartof><rights>Copyright © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved 2012</rights><rights>2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved</rights><rights>2015 INIST-CNRS</rights><rights>2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.</rights><rights>Copyright © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. 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Phosphatidylcholine (PC) is the major phospholipid in eukaryotes and an essential component of cell membranes playing structural, biochemical, and physiological roles. However, in prokaryotes, PC is present only in those species closely associated with eukaryotes, either in symbiotic or pathogenic interactions. In trypanosomatids, the endosymbiont envelope is composed by a reduced cell wall and by two membrane units that lack sterols and present cardiolipin (CL) and PC as the major phospholipids. In this study, we tested the effects of miltefosine in A. deanei proliferation, as well as, on the ultrastrucuture and phospholipid composition considering that this drug inhibits the CTP-phosphocholine cytidyltransferase (CCT), a key enzyme in the PC biosynthesis. Besides the low effect of miltefosine in cellular proliferation, treated protozoa presented ultrastructural alterations such as plasma membrane shedding and blebbing, mitochondrial swelling, and convolutions of the endosymbiont envelope. The use of 32Pi as a tracer revealed that the production of PC, CL, and phosphatidylethanolamine decreased while phosphatidylinositol production remained stable. Mitochondrion and symbiont fractions obtained from protozoa treated with miltefosine also presented a decrease in phospholipid production, reinforcing the idea that an intensive metabolic exchange occurs between the host trypanosomatid and structures of symbiotic origin.</description><subject>Angomonas deanei</subject><subject>Bacteria</subject><subject>Bacteria - drug effects</subject><subject>Bacteria - growth &amp; development</subject><subject>Biological and medical sciences</subject><subject>Biosynthesis</subject><subject>Cardiolipin</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Membrane - ultrastructure</subject><subject>Cell membranes</subject><subject>Cell Wall - drug effects</subject><subject>Cell Wall - metabolism</subject><subject>Cell walls</subject><subject>Choline-Phosphate Cytidylyltransferase - metabolism</subject><subject>Composition</subject><subject>Crithidia - drug effects</subject><subject>Crithidia - metabolism</subject><subject>Crithidia - microbiology</subject><subject>Crithidia - ultrastructure</subject><subject>endosymbiosis</subject><subject>Eukaryotes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Lecithin</subject><subject>Microbiology</subject><subject>Microscopy, Electron, Transmission</subject><subject>Miltefosine</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - ultrastructure</subject><subject>Phosphatidylcholine</subject><subject>Phosphatidylcholines - biosynthesis</subject><subject>Phosphatidylethanolamine</subject><subject>Phosphatidylinositol</subject><subject>Phosphocholine</subject><subject>phospholipid biosynthesis</subject><subject>Phospholipid composition</subject><subject>Phospholipids</subject><subject>Phosphorus Isotopes - metabolism</subject><subject>Phosphorylcholine - analogs &amp; derivatives</subject><subject>Phosphorylcholine - pharmacology</subject><subject>Prokaryotes</subject><subject>Protozoa</subject><subject>Sterols</subject><subject>Symbiosis</subject><subject>trypanosomatid protozoa</subject><subject>Ultrastructure</subject><issn>0378-1097</issn><issn>1574-6968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkd-K1DAYxYMo7rj6ChIQwYttzZ82SS-8WJZdFUa80euQpomToU1qkrI7PpMPaeqMKyiChdCE_M75TjgAQIxqXL7X-xq3vKlYx0RNECY1Igzx-u4B2NxfPAQbRLmoMOr4GXiS0h4h1BDEHoMzQliLRUs34Pu1tUbnBIOFkxuzsSE5b2DwMO8MnGMYnTVRZRf8BVzGHFXKcdF5ieYCKj_AeRdSWaOb3QB1mOZisNKr46X_EqbgVYKDUd64ooA5HmblQwpTMR3WCTl8C2qdpzLcqdiHmAqXDlPvQnYa9kpnE90yPQWPrBqTeXb6n4PPN9efrt5V249v319dbivdcMwrMvTGMoYbwhmjWHcEG9qgoWu4EoIN1HJhGoopweWg2gYR0akem05ZbRin5-DV0beE-7qYlOXkkjbjWN4QliRxESAsiGAFffEHug9L9CWdJBS1vCsQLpQ4UjqGlKKxco5uUvFQrOTaqNzLtTi5FifXRuXPRuVdkT4_DVj6yQz3wl8VFuDlCVBJq9FG5bVLvzmGWyS6tnBvjtytG83hvwPImw_bdVf09KgPy_wPdfV3_B8HMM52</recordid><startdate>201208</startdate><enddate>201208</enddate><creator>de Freitas-Junior, Paulo R.G.</creator><creator>Catta-Preta, Carolina M.C.</creator><creator>Andrade, Iamara da Silva</creator><creator>Cavalcanti, Danielle P.</creator><creator>de Souza, Wanderley</creator><creator>Einicker-Lamas, Marcelo</creator><creator>Motta, Maria Cristina M.</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</general><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201208</creationdate><title>Effects of miltefosine on the proliferation, ultrastructure, and phospholipid composition of Angomonas deanei, a trypanosomatid protozoan that harbors a symbiotic bacterium</title><author>de Freitas-Junior, Paulo R.G. ; Catta-Preta, Carolina M.C. ; Andrade, Iamara da Silva ; Cavalcanti, Danielle P. ; de Souza, Wanderley ; Einicker-Lamas, Marcelo ; Motta, Maria Cristina M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4717-2dbef6614276631c921e340d947a886d3f78e4313216d3a540289ab1e9afce673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Angomonas deanei</topic><topic>Bacteria</topic><topic>Bacteria - drug effects</topic><topic>Bacteria - growth &amp; development</topic><topic>Biological and medical sciences</topic><topic>Biosynthesis</topic><topic>Cardiolipin</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Membrane - ultrastructure</topic><topic>Cell membranes</topic><topic>Cell Wall - drug effects</topic><topic>Cell Wall - metabolism</topic><topic>Cell walls</topic><topic>Choline-Phosphate Cytidylyltransferase - metabolism</topic><topic>Composition</topic><topic>Crithidia - drug effects</topic><topic>Crithidia - metabolism</topic><topic>Crithidia - microbiology</topic><topic>Crithidia - ultrastructure</topic><topic>endosymbiosis</topic><topic>Eukaryotes</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Lecithin</topic><topic>Microbiology</topic><topic>Microscopy, Electron, Transmission</topic><topic>Miltefosine</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - ultrastructure</topic><topic>Phosphatidylcholine</topic><topic>Phosphatidylcholines - biosynthesis</topic><topic>Phosphatidylethanolamine</topic><topic>Phosphatidylinositol</topic><topic>Phosphocholine</topic><topic>phospholipid biosynthesis</topic><topic>Phospholipid composition</topic><topic>Phospholipids</topic><topic>Phosphorus Isotopes - metabolism</topic><topic>Phosphorylcholine - analogs &amp; derivatives</topic><topic>Phosphorylcholine - pharmacology</topic><topic>Prokaryotes</topic><topic>Protozoa</topic><topic>Sterols</topic><topic>Symbiosis</topic><topic>trypanosomatid protozoa</topic><topic>Ultrastructure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Freitas-Junior, Paulo R.G.</creatorcontrib><creatorcontrib>Catta-Preta, Carolina M.C.</creatorcontrib><creatorcontrib>Andrade, Iamara da Silva</creatorcontrib><creatorcontrib>Cavalcanti, Danielle P.</creatorcontrib><creatorcontrib>de Souza, Wanderley</creatorcontrib><creatorcontrib>Einicker-Lamas, Marcelo</creatorcontrib><creatorcontrib>Motta, Maria Cristina M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; 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Phosphatidylcholine (PC) is the major phospholipid in eukaryotes and an essential component of cell membranes playing structural, biochemical, and physiological roles. However, in prokaryotes, PC is present only in those species closely associated with eukaryotes, either in symbiotic or pathogenic interactions. In trypanosomatids, the endosymbiont envelope is composed by a reduced cell wall and by two membrane units that lack sterols and present cardiolipin (CL) and PC as the major phospholipids. In this study, we tested the effects of miltefosine in A. deanei proliferation, as well as, on the ultrastrucuture and phospholipid composition considering that this drug inhibits the CTP-phosphocholine cytidyltransferase (CCT), a key enzyme in the PC biosynthesis. Besides the low effect of miltefosine in cellular proliferation, treated protozoa presented ultrastructural alterations such as plasma membrane shedding and blebbing, mitochondrial swelling, and convolutions of the endosymbiont envelope. The use of 32Pi as a tracer revealed that the production of PC, CL, and phosphatidylethanolamine decreased while phosphatidylinositol production remained stable. Mitochondrion and symbiont fractions obtained from protozoa treated with miltefosine also presented a decrease in phospholipid production, reinforcing the idea that an intensive metabolic exchange occurs between the host trypanosomatid and structures of symbiotic origin.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22651853</pmid><doi>10.1111/j.1574-6968.2012.02607.x</doi><tpages>9</tpages></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Angomonas deanei
Bacteria
Bacteria - drug effects
Bacteria - growth & development
Biological and medical sciences
Biosynthesis
Cardiolipin
Cell Membrane - drug effects
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cell membranes
Cell Wall - drug effects
Cell Wall - metabolism
Cell walls
Choline-Phosphate Cytidylyltransferase - metabolism
Composition
Crithidia - drug effects
Crithidia - metabolism
Crithidia - microbiology
Crithidia - ultrastructure
endosymbiosis
Eukaryotes
Fundamental and applied biological sciences. Psychology
Lecithin
Microbiology
Microscopy, Electron, Transmission
Miltefosine
Mitochondria
Mitochondria - drug effects
Mitochondria - ultrastructure
Phosphatidylcholine
Phosphatidylcholines - biosynthesis
Phosphatidylethanolamine
Phosphatidylinositol
Phosphocholine
phospholipid biosynthesis
Phospholipid composition
Phospholipids
Phosphorus Isotopes - metabolism
Phosphorylcholine - analogs & derivatives
Phosphorylcholine - pharmacology
Prokaryotes
Protozoa
Sterols
Symbiosis
trypanosomatid protozoa
Ultrastructure
title Effects of miltefosine on the proliferation, ultrastructure, and phospholipid composition of Angomonas deanei, a trypanosomatid protozoan that harbors a symbiotic bacterium
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