Targeting lipid biosynthesis and salvage in apicomplexan parasites for improved chemotherapies

被引:73
作者
Coppens, Isabelle [1 ]
机构
[1] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
DIPHOSPHATE/GERANYLGERANYL-DIPHOSPHATE SYNTHASE; METHYLERYTHRITOL PHOSPHATE-PATHWAY; HIGH-DENSITY-LIPOPROTEINS; PLASMODIUM LIVER-STAGE; TOXOPLASMA-GONDII; ISOPRENOID BIOSYNTHESIS; DE-NOVO; INTRAERYTHROCYTIC STAGES; CHOLESTEROL ABSORPTION; SPHINGOLIPID SYNTHESIS;
D O I
10.1038/nrmicro3139
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Apicomplexa are some of the most widespread and poorly controlled pathogens in the world. The metabolism of lipids in these parasites, which include Plasmodium spp., Toxoplasma gondii and Cryptosporidium spp., is essential for the production of infectious progeny and pathogen persistence in their mammalian hosts. Metabolic maps of apicomplexan lipid syntheses reveal auxotrophies for many lipid species, which force these parasites to meet their high demand for lipids through networks of both synthesis and scavenging. Here, I review the unique lipid biosynthetic enzymes and lipid transporter systems of Apicomplexa, focusing on isoprenoids, sphingolipids and cholesterol, and highlight promising chemotherapeutic targets in the lipid synthetic and salvage pathways.
引用
收藏
页码:823 / 835
页数:13
相关论文
共 128 条
[101]   The economic and social burden of malaria [J].
Sachs, J ;
Malaney, P .
NATURE, 2002, 415 (6872) :680-685
[102]   Localization and role of NPC1L1 in cholesterol absorption in human intestine [J].
Sane, Alain Theophile ;
Sinnett, Daniel ;
Delvin, Edgard ;
Bendayan, Moise ;
Marcil, Valerie ;
Menard, Daniel ;
Beaulieu, Jean-Francois ;
Levy, Emile .
JOURNAL OF LIPID RESEARCH, 2006, 47 (10) :2112-2120
[103]   Giardia and Cryptosporidium join the 'Neglected Diseases Initiative' [J].
Savioli, L. ;
Smith, H. ;
Thompson, A. .
TRENDS IN PARASITOLOGY, 2006, 22 (05) :203-208
[104]   METABOLIC PATHWAYS IN THE APICOPLAST OF APICOMPLEXA [J].
Seeber, Frank ;
Soldati-Favre, Dominique .
INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 281, 2010, 281 :161-228
[105]   Peculiarities of host cholesterol transport to the unique intracellular vacuole containing Toxoplasma [J].
Sehgal, A ;
Bettiol, S ;
Pypaert, M ;
Wenk, MR ;
Kaasch, A ;
Blader, IJ ;
Joiner, KA ;
Coppens, I .
TRAFFIC, 2005, 6 (12) :1125-1141
[106]  
Sinai AP, 1997, J CELL SCI, V110, P2117
[107]   Lipophilic Bisphosphonates Are Potent Inhibitors of Plasmodium Liver-Stage Growth [J].
Singh, Agam Prasad ;
Zhang, Yonghui ;
No, Joo-Hwan ;
Docampo, Roberto ;
Nussenzweig, Victor ;
Oldfield, Eric .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (07) :2987-2993
[108]   BIOSYNTHESIS OF UBIQUINONES BY MALARIAL PARASITES .I. ISOLATION OF [14C]UBIQUINONES FROM CULTURES OF RHESUS MONKEY BLOOD INFECTED WITH PLASMODIUM KNOWLESI [J].
SKELTON, FS ;
LUNAN, KD ;
FOLKERS, K ;
SCHNELL, JV ;
SIDDIQUI, WA ;
GEIMAN, QM .
BIOCHEMISTRY, 1969, 8 (03) :1284-&
[109]  
Snow RW, 2005, NATURE, V434, P214, DOI 10.1038/nature03342
[110]   Inhibitory effect of aureobasidin A on Toxoplasma gondii [J].
Sonda, S ;
Sala, G ;
Ghidoni, R ;
Hemphill, A ;
Pieters, J .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (05) :1794-1801