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INDEX 475 energy metabolism, 145 genome, 20 HSP genes, 81 lipophosphoglycan (LPG) mutants, 115 promoter structures, 53, 54 purine metabolism, 198, 212–14 transport, 198, 203, 204 secreted acid phosphatase, 237 surface glycoconjugates: glycosylinositolphospholipids, 235 GP63, 236 lipophosphoglycan, 232, 233, 234 manan-like carbohydrate, 237 membrane-bound acid phosphatase, 237 virulence candidate genes, 119 Leishmania infantum: HSP genes, 81 polyamines synthesis, 191 Leishmania major: acidocalcisomes, 249 amastigote-specific proteophosphoglycan, 239 amino acid metabolism, 192 osmotic stress responses, 193 avirulence genetic rescue, 116 cAMP-dependent protein kinase (PKA), 261 genome, 20–1, 73, 118 glycosylinositolphospholipids, 235 GP63, 236 HSP genes, 81 lipophosphoglycan, 232, 233, 234 polycistronic transcription of protein coding genes, 49 proteolytic enzymes, 177 proteophosphoglycan, 239 purine transport, 204 reference strain, 13 virulence candidate genes, 119, 120 Leishmania mexicana: amino acid metabolism, 192 catabolism, 188 CDK-related kinases (CRKs), 271 digestive organelles, 180 energy metabolism, 146, 147, 148, 150 therapeutic targets, 146–7 glycosylinositolphospholipids, 235 GP63, 236 lipophosphoglycan, 232, 233 mitogen-activated protein (MAP) kinases, 269 proteolytic enzymes, 174, 175, 180 20S proteasome, 177 secreted acid phosphatase, 237 virulence candidate genes, 119, 120 Leishmania tarentolae: kinetoplast RNA (kRNA) editing, 39, 40 spliced leader (SL) RNA gene promoter, 61 Leishmania tropica: amino acid metabolism, 192 lipophosphoglycan, 233 secreted acid phosphatase, 237 Leishmanolysin, see Gp63 Leptomonas samueli, 235 Leptomonas seymouri,61 let-653, 337 Leucine, lipid synthesis, 191–2 lev-1, 371 Levamisole: absorption, 326 mode of action, 359, 360, 368, 369, 370 resistance, 371, 428 structure, 359 Ligula intestinalis, 301 lin-4, 316 lin-14, 316 lin-15, 372 lin-28, 316 lin-29, 316 Lipase, 329, 330 Lipid synthesis, 191–2 Lipopeptidophosphoglycan, 230–1 glycosylphosphatidylinositol (GPI) anchors, 230–1 structure, 229, 230–1 Lipophosphoglycan, 112, 114–15, 231–5 developmentally regulated expression, 234 metacyclogenesis, 233–4 functions, 234–5 glycosylphosphatidylinositol (GPI) anchors, 115 lipid anchor, 233 mutants, 115 structure, 231, 232–3 Liposomal amphotericin B, 451 Lmaa, 1, 246, 247 lmcpa, 175 lmcpc, 175 LmNT3, 204 Loa loa, 457, 458 LPG1, 120 LPG2, 120 LRP-1, 316 Lysosomal proteolytic enzymes, 175
476 INDEX Maduramicin, 412 Major variant erythrocyte surface proteins, 107 Malaria, see Plasmodium Malate:ubiquinone oxidoreductase, 164–5 Malate dehydrogenase, 130, 164 Maltase, 329, 330 Manan-like carbohydrate, 237 Mannitol 1-phosphatase, 167 Mannitol 1-phosphate dehydrogenase, 166–7 inhibitors, 167–8 Mannitol cycle, 166, 168 Mannitol dehydrogenase, 167 Mansonella streptocerca, 458 Map-based genome sequencing, 10–11 MDR1, 417 mdr1a, 333 Mebendazole, 460 mec-8, 317, 318 Mefloquine, 440, 441, 442, 443–5 resistance, 406–7, 443 structure, 401, 440 Megasome, 180 Megazol, 432 Meglumine antimonate, 413, 451 Melarsen oxide, 147 Melarsoprol, 412, 419, 430, 448, 450 mode of action, 419 resistance, 419, 448 Meloidogyne,20 Membrane-bound acid phosphatase, 237 Mesocestoides corti, 392 Metagonimus yokogawi, 458 Metalloproteinases, 174, 176–7, 178, 179, 180 Methionine: catabolism, 185, 186 polyamines synthesis, 189–91 recycling, 185, 186 Methionine adenosyltransferase, 191 Methionine -lyase, 185 Methotrexate resistance, 418 Methylene blue dye, 439, 440 5 Methylthioadenosine (MTA) nucleosidase, 185 5 Methylthioadenosine (MTA) phosphorylase, 185 5-Methylthioribose kinase, 185 Methyridine, 368 Metorchis conjunctus, 458 Metrifonate (trichlorfon), 367, 389 Metronidazole, 432, 438, 453–4 mode of action, 135, 284, 453 resistance: Entamoeba histolytica, 426 Giardia duodenaslis, 425 Trichomonas vaginalis, 424–5 structure, 414 Microaerophilic organisms, 126 Microsporidia, 125, 283 Microtriches, 298 biochemistry/molecular biology, 299 Miltefosine, 414, 452, 453 resistance, 417 Mitochondria, 277 Ca 2 transport, 242, 243–5 endosymbiosis: reduction processes, 279–80 theory, 277–9 kinetoplastids, 281–2 metabolism, 280–2 drug targets, 281 Plasmodium, 281 targeting of nucleus encoded gene products, 280 Mitochondrial energy metabolism, 278 helminths, 339–40, 344–53, 354 Plasmodium falciparum, 161–5 citric acid (TCA) cycle, 164–5 electron transport, 161–3 oxidative phosphorylation, 163–4 Mitochondrial genome, 278 evolutionary reduction, 279 intracellular gene transfer, 279–80 nematodes, 25 Plasmodium, 161, 281 RNA editing processes, 38 see also Kinetoplast Mitogen-activated protein (MAP) kinase: gene expression regulation, 268 intracellular signaling, 266–70 protozoan parasites, 268–70 apicomplexans, 268–9 Giardia, 168, 270 kinetoplastids, 269–70 scaffold proteins, 267 three-kinase activation, 266–7 Mitosome (cryptome), 126, 282 Monesia expansa, 392 Monesin, 412 Moniezia benedeni, 222 Morantel, 368
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Molecular Medical Parasitology
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Molecular Medical Parasitology Edit
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Contents List of contributors Prefa
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List of contributors Mark Blaxter,
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LIST OF CONTRIBUTORS ix Richard. J.
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Preface Parasitology was born as th
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S E C T I O N I MOLECULAR BIOLOGY
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C H A P T E R 1 Parasite genomics M
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TABLE 1.1 Parasite genomes: genome
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GENERATING GENOMICS DATA 7 differen
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GENERATING GENOMICS DATA 9 TABLE 1.
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GENERATING GENOMICS DATA 11 called
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GENERATING GENOMICS DATA 13 200 000
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BIOINFORMATICS AND THE ANALYSIS OF
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THE POST-GENOMICS ERA, AND THE OTHE
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THE PARASITES AND THEIR GENOMES 19
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FURTHER READING 27 treated with a d
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C H A P T E R 2 RNA processing in p
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TRANS-SPLICING 31 cis trans Exon 1
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TRANS-SPLICING 33 snRNPs (small nuc
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TRANS-SPLICING 35 trans cis U2AF35
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RNA EDITING 37 P AAAA... AAAA... AA
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RNA EDITING 39 entire transcript re
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RNA EDITING 41 5 Editing block C Ed
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RNA EDITING 43 microscopy) approach
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FURTHER READING 45 Nilsen, T.W. (19
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C H A P T E R 3 Transcription Arthu
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UNUSUAL MODES OF TRANSCRIPTION IN T
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CLASS I TRANSCRIPTION IN TRYPANOSOM
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CLASS II TRANSCRIPTION OF PROTEIN C
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SL RNA AND U snRNA GENE TRANSCRIPTI
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FURTHER READING 65 and switching in
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C H A P T E R 4 Post-transcriptiona
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POST-TRANSCRIPTIONAL REGULATION IN
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FURTHER READING 87 inhibition, it m
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C H A P T E R 5 Antigenic variation
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ANTIGENIC VARIATION AT THE STRUCTUR
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ANTIGENIC VARIATION AT THE STRUCTUR
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VSG Signal sequence Amino-terminal
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GENETICS OF ANTIGENIC VARIATION 97
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IMMUNE RESPONSES TO TRYPANOSOME INF
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INNATE RESISTANCE, HUMAN SUSCEPTIBI
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ANTIGENIC VARIATION IN MALARIA 107
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FURTHER READING 109 ACKNOWLEDGEMENT
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C H A P T E R 6 Genetic and genomic
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‘FORWARD’ VS. ‘REVERSE’ GEN
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EXAMPLES OF ‘FORWARD’ GENETIC A
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EXAMPLES OF ‘FORWARD’ GENETIC A
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REVERSE GENETICS AND LEISHMANIA VIR
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VALIDATION OF CANDIDATE VIRULENCE G
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S E C T I O N II BIOCHEMISTRY AND C
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C H A P T E R 7 Energy metabolism P
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SUBCELLULAR ORGANIZATION OF AMITOCH
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CELL MEMBRANE Fructose [b] Glucose
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STEPS OF AMITOCHONDRIATE CORE METAB
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ENZYMATIC DIFFERENCES BETWEEN AMITO
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ACTION OF NITROIMIDAZOLE DRUGS 135
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ENVOI 137 unambiguously reflect the
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FURTHER READING 139 Saavedra-Lira,
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THE EMBDEN-MEYERHOF-PARNAS (EMP) PA
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WHY DO TRYPANOSOMATIDAE HAVE GLYCOS
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FURTHER READING 153 for use in agri
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CARBOHYDRATE METABOLISM 155 as a hu
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158 ENERGY METABOLISM - APICOMPLEXA
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172 PROTEIN METABOLISM PROTEINS (1)
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174 PROTEIN METABOLISM the C-termin
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176 PROTEIN METABOLISM and also, to
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178 PROTEIN METABOLISM values rangi
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180 PROTEIN METABOLISM of the plasm
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182 PROTEIN METABOLISM in vivo, in
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184 PROTEIN METABOLISM PROLINE Poly
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186 PROTEIN METABOLISM CO 2 Dec-SAM
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188 PROTEIN METABOLISM a cMDH has b
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190 PROTEIN METABOLISM Urea ARGININ
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192 PROTEIN METABOLISM been describ
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194 PROTEIN METABOLISM absence of g
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198 PURINES AND PYRIMIDINES enable
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200 PURINES AND PYRIMIDINES provide
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202 PURINES AND PYRIMIDINES activit
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204 PURINES AND PYRIMIDINES physiol
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206 PURINES AND PYRIMIDINES Amitoch
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208 PURINES AND PYRIMIDINES their a
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210 PURINES AND PYRIMIDINES FIGURE
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214 PURINES AND PYRIMIDINES protein
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220 PURINES AND PYRIMIDINES in Plas
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222 PURINES AND PYRIMIDINES whereas
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226 TRYPANOSOMATID CARBOHYDRATES AF
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228 TRYPANOSOMATID CARBOHYDRATES In
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230 TRYPANOSOMATID CARBOHYDRATES po
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232 TRYPANOSOMATID CARBOHYDRATES LP
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234 TRYPANOSOMATID CARBOHYDRATES re
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236 TRYPANOSOMATID CARBOHYDRATES sc
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A. sAP COOH [T][T](S/T)(S/T)(S/T)SS
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240 TRYPANOSOMATID CARBOHYDRATES Cr
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242 INTRACELLULAR SIGNALING protein
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244 INTRACELLULAR SIGNALING FIGURE
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246 INTRACELLULAR SIGNALING 212.5 2
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248 INTRACELLULAR SIGNALING cycle.
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250 INTRACELLULAR SIGNALING V-H -A
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252 INTRACELLULAR SIGNALING domain)
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254 INTRACELLULAR SIGNALING the kno
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256 INTRACELLULAR SIGNALING from in
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258 INTRACELLULAR SIGNALING FIGURE
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260 INTRACELLULAR SIGNALING ESAG4 (
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262 INTRACELLULAR SIGNALING and ind
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264 INTRACELLULAR SIGNALING ATPase
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266 INTRACELLULAR SIGNALING G11XG
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268 INTRACELLULAR SIGNALING a diffe
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270 INTRACELLULAR SIGNALING rapid l
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272 INTRACELLULAR SIGNALING cells w
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274 INTRACELLULAR SIGNALING PfPPJ i
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276 INTRACELLULAR SIGNALING is cont
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278 PLASTIDS, MITOCHONDRIA, AND HYD
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298 HELMINTH SURFACES Important exc
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300 HELMINTH SURFACES protease inhi
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302 HELMINTH SURFACES volume, there
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304 HELMINTH SURFACES projecting si
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306 HELMINTH SURFACES schistosome t
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308 HELMINTH SURFACES re-establish
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310 HELMINTH SURFACES hepatic cells
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312 HELMINTH SURFACES lungs. Larvae
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314 HELMINTH SURFACES cuticle, whic
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316 HELMINTH SURFACES cuticle in th
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318 HELMINTH SURFACES mec-8 or sym-
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320 HELMINTH SURFACES current, when
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322 HELMINTH SURFACES The cuticle-h
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324 HELMINTH SURFACES are typically
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326 HELMINTH SURFACES or carrier pr
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328 HELMINTH SURFACES of tyrosine-b
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330 HELMINTH SURFACES blood. The ge
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332 HELMINTH SURFACES Mutations in
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334 HELMINTH SURFACES in the hypode
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336 HELMINTH SURFACES (including H-
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338 HELMINTH SURFACES Blaxter, M.L.
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340 ENERGY METABOLISM IN HELMINTHS
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360 NEUROTRANSMITTERS CO 2 H NH 2 G
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362 NEUROTRANSMITTERS TABLE 15.1 An
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364 NEUROTRANSMITTERS more arms tha
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366 NEUROTRANSMITTERS the surroundi
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368 NEUROTRANSMITTERS proteins requ
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370 NEUROTRANSMITTERS FIGURE 15.11
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372 NEUROTRANSMITTERS FIGURE 15.13
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374 NEUROTRANSMITTERS sensitivity t
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376 NEUROTRANSMITTERS TABLE 15.3 Cl
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378 NEUROTRANSMITTERS crossed the c
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380 NEUROTRANSMITTERS have been tes
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382 NEUROTRANSMITTERS C-terminals a
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384 NEUROTRANSMITTERS Davis and Str
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386 NEUROTRANSMITTERS Cephalic gang
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388 NEUROTRANSMITTERS myoexcitation
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390 NEUROTRANSMITTERS is phosphoryl
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392 NEUROTRANSMITTERS many other an
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398 DRUG RESISTANCE of some of the
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400 DRUG RESISTANCE It is now estim
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402 DRUG RESISTANCE is again assume
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404 DRUG RESISTANCE An alternative
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406 DRUG RESISTANCE clinical eviden
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408 DRUG RESISTANCE FIGURE 16.4 Fol
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410 DRUG RESISTANCE Using similar s
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412 DRUG RESISTANCE whether these r
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414 DRUG RESISTANCE FIGURE 16.5 Str
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416 DRUG RESISTANCE FIGURE 16.6 Try
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418 DRUG RESISTANCE has permitted e
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420 DRUG RESISTANCE FIGURE 16.7 Dru
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422 DRUG RESISTANCE near future. Th
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Page 441 and 442: 428 DRUG RESISTANCE pharynx, the bo
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Page 445 and 446: 432 DRUG RESISTANCE and resistance
Page 447 and 448: 434 MEDICAL IMPLICATIONS TABLE 17.1
Page 449 and 450: 436 MEDICAL IMPLICATIONS TABLE 17.1
Page 451 and 452: 438 MEDICAL IMPLICATIONS transmissi
Page 453 and 454: 440 MEDICAL IMPLICATIONS H 2 C H H
Page 455 and 456: 442 MEDICAL IMPLICATIONS parasites
Page 457 and 458: 444 MEDICAL IMPLICATIONS neuropsych
Page 459 and 460: 446 MEDICAL IMPLICATIONS of toxic f
Page 461 and 462: 448 MEDICAL IMPLICATIONS Future con
Page 463 and 464: 450 MEDICAL IMPLICATIONS Melarsopro
Page 465 and 466: 452 MEDICAL IMPLICATIONS prevention
Page 467 and 468: 454 MEDICAL IMPLICATIONS resulting
Page 469 and 470: 456 MEDICAL IMPLICATIONS for S. ste
Page 471 and 472: 458 MEDICAL IMPLICATIONS are though
Page 473 and 474: 460 MEDICAL IMPLICATIONS FIGURE 17.
Page 475 and 476: 462 MEDICAL IMPLICATIONS Marr, J.J.
Page 477 and 478: 464 INDEX Aldolase, 143 Plasmodium
Page 479 and 480: 466 INDEX Ascofuranone, 143 ASCUT-1
Page 481 and 482: 468 INDEX Cnidarians, RNA trans-spl
Page 483 and 484: 470 INDEX Entamoeba, 125 Ca 2 metab
Page 485 and 486: 472 INDEX Glucose-6-phosphate dehyd
Page 487: 474 INDEX Ivermectin, 398, 427, 455
Page 491 and 492: 478 INDEX Nitric oxide: neurotransm
Page 493 and 494: 480 INDEX calcium-binding proteins,
Page 495 and 496: 482 INDEX Pyrimidine transport, 200
Page 497 and 498: 484 INDEX Succinate:rhodoquinone ox
Page 499 and 500: 486 INDEX genome, 21 survey sequenc
Page 501: 488 INDEX U small nuclear RNA (snRN
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