BOOK REVIEWS INTERNATIONAL MICROBIOLOGY (2005) 8:71-76 www.im.microbios.org Malaria Parasites. mosomes. The following chapter (The genome of model Genomes and malaria parasites, and comparative genomics, by J. Carlton, J. Molecular Biology Silva, and N. Hall) explores general aspects of the compara- tive genomics and chromosome structure of P. falciparum and other protozoans from the same genus, including P. ANDREW P. WATERS, vivax, P. yoelii, P. chabaudi, P. berghei, and P. knowlesi. Com- CHRIS J. JANSE (EDS) plementing the data provided in those chapters, A. Scherf, 2004. Caister Academic Press, Norfolk, UK L.M. Figueiredo, and L.H. Freitas, Jr., present an in-depth 546 pp, 24 × 16 cm study of the subtelomeric regions of the Plasmodium chromo- Price: US$ 230 ISBN 0-9542464-6-2 somes (Chap. 7). In Chap. 8, there is another excellent review, by K.W. Deitsch, on the regulation of gene expression in Plasmodium, in which both the epigenetic control of gene expression and the transcriptional control of the var genes, responsible for antigenic variation and escape of the parasite The book Malaria Parasites: Genomes and Molecular from the host’s immune response, are emphasized. The Biology presents an overview of the tasks that were involved genome analyses carried out thus far have been limited com- in obtaining and deciphering parasite DNA sequences that pared to the promise of those that can be done on whole led to the completion of the Plasmodium falciparum Genome genomes of the various malaria parasites that have already been Project. It represents a complete guide for researchers inter- sequenced or that are currently in development. In Chap. 3, J.C. ested in genome analysis and the molecular biology of P. fal- Kissinger and D.S. Roos describe how these data can be ciparum and other Plasmodium parasites. The information exploited and the corresponding bioinformatics resources that gathered in the 16 chapters, authored by well-known special- will be essential for such analyses. The strength and weakness ists in the corresponding fields, is of great relevance for read- of these methods and the requirements for a critical evaluation ers interested in anti-malaria vaccine development, drug dis- of the results are discussed. covery, and the analysis of parasite genes and proteins using Working knowledge of the tools necessary to manipulate bioinformatics, as well as in understanding the biology of the expression of parasite genes is important to be able to Plasmodium and related parasites. identify their functions. In Chap. 4, T. Gil Carvalho and R. The Introduction transmits a sense of the tremendous Ménard describe different ways to examine gene function effort, in terms of funding and human and technical that have been or have the potential to be applied to Plasmo- resources, that the P. falciparum Genome Project required. dium. The authors show how the technology to genetically Five institutions, initially, the Burroughs Wellcome Fund, the transform the parasites in order to study gene function or pro- National Institute of Allergy and Infectious Diseases moter activity has evolved since the first report of parasite (NIAID), the US Department of Defense, and the Wellcome transfection was published, in 1993. Toxoplasma gondii is a Trust, later joined by the World Health Organization, provid- Plasmodium-related Apicomplexa parasite. In Chap. 5, D. ed the funds. Four other centers, the Sanger Center, Stanford Soldati and M. Meissner offer insight into how classes of University, The Institute for Genomic Research (TIGR), and genes unique to this phylum can be analyzed in T. gondii, the US Naval Medical Research Center (NMRC) provided aiming at a possible identification of common targets for the infrastructure as well as the personnel. From the start, the intervention. Experimental approaches for genetic and bio- results of the project were quickly made available through logical research on T. gondii are also described. It is worth the PlasmoDB database [http://PlasmoDB.org], and stan- mentioning that the results of the T. gondii sequencing project dardized reagents related to the ongoing research, and to can also be consulted in the corresponding database website malaria research in general, could be obtained through the [http://ToxoDB.org]. The genomic analysis of P. falciparum establishment of the Malaria Research and Reference has revealed an abundance of microsatellite (MS) markers. Reagent Resource (MR4). These are useful for dissecting gene function, identifying vac- In the first chapter, N. Hall and M. Gardner describe the cine candidates and drug targets, and elucidating the evolution- beginnings of the Plasmodium falciparum Genome Project— ary history of the parasites. In Chap. 6, D. Joy, J. Mu, and X. the first large-scale genetic analysis of a eukaryotic pathogen— Su present an overview of the MS markers of P. falciparum and the final results of the sequencing of the organism’s 14 chro- and their applications in studying population genetics. 72 INT. MICROBIOL. Vol. 8, 2004 BOOK REVIEWS One feature of Plasmodium parasites, already known well Chapter 14, written by the editors of the book, C.J. Janse before the completion of the Genome Project, is that they and A.P. Waters, discusses the sexual development of the par- express structurally distinct sets of rRNA depending on their asite and the possibility of generating a transmission-block- developmental stage. This has a profound effect on the abili- ing vaccine that, by targeting proteins expressed during the ty of the parasite to synthesize proteins and on its capacity to sexual stages or by the zygote, would interrupt the life cycle progress to the next stage of its life cycle. In Chap. 9, T.F. of the parasites during their final stages inside the mam- McCutchan, R. van Sapendonk, C. Janse, J. Fang, and A.P. malian host. This approach is further discussed in Chap. 15 Waters review the different rRNAs, focusing on regulation of (by R.E. Sidden et al.), which deals with formation of the their transcription and processing during the parasite life ookinete from the zygote, invasion of the mosquito midgut, cycle. Chapter 10 deals with the control of the parasite cell formation of the new oocyst, and the possibilities for inter- cycle in the different developmental stages. C. Doerig and D. ruption of these processes by using an ookinete-derived Chakrabarti explain how the complex multi-stage life cycle transmission-blocking vaccine or by administering anti- of the parasite progresses, and the involvement of cyclins, malarial drugs that would target the sporogonic stages. The cyclin-dependent kinases, and other factors in controlling final chapter, by K. L. Waller, S. Lee, and D.A. Fidock, is this progression. One of the most distinctive features of the devoted to the resistance of P. falciparum to the drug that has organisms of the phylum Apicomplexa is the existence of an been considered the gold standard in the treatment of malar- intracellular ancient endosymbiont, known as the apicoplast. ia for more than 50 years: chloroquine. A mechanistic model This semi-autonomous organelle has its own genome and of resistance is provided and several key questions are raised, expression machinery and is involved in several metabolic the answerers to which will provide a better understanding of routes, making it an excellent target for anti-parasitic drug the mechanism of resistance to chloroquine as well as to development, as explained in detail in Chap. 11 by R.F. other quinoline drugs and related antimalarials. Waller and G.I. McFadden. The apicoplast’s interesting struc- The book presented here offers a first-rate overview of ture, phylogenetic origin (a red alga), function, contents, pro- the current status of Plasmodium and malaria research, tein-targeting properties, and mechanisms of transmission to reviewing the answers that specialists have given to key ques- Plasmodium progeny are also described. tions raised about these parasites and the devastating disease Plasmodium parasites interact with a wide variety of host they cause, through the analysis of the genome and the cells during their life cycle via ligands displayed by the para- molecular biology of P. falciparum and other species of site that specifically bind to counterparts on the surfaces of Plasmodium. Although we highly recommend this book, data host cells. These molecules are good candidates for vaccine related to one of the key stages for intervention against development since immune responses mounted against them malaria, i.e. sporozoites, are somehow missing. Sporozoites could protect the host organism from infection. In Chap. 12, are the initial infective forms of Plasmodium, and their elim- J.D. Smith and A.G. Craig review the features of these impor- ination would prevent the development of malaria. tant molecules and the mechanisms of antigenic variation Hopefully, a discussion of sporozoites will appear in the next that the parasite has developed to evade immune recognition. edition of this book, thereby further broadening readers’ A vaccine directed against the blood stages of Plasmodium knowledge about this parasite, which is presently one of the will not prevent infection by the parasite but will attenuate or main infectiuos killers of the human species. eliminate the symptoms associated with malaria, a therapeu- tic strategy much needed by inhabitants of countries con- stantly exposed to such a threat. The merozoite is the only form among the blood stages of the parasite that is found in OSCAR BRUÑA-ROMERO1 the blood-stream outside host cells. Thus, an efficient WANDERSON D. DAROCHA2 immune response to the merozoite or new drugs targeted 1Universidade Federal de Minas Gerais against it will impede erythrocyte invasion, thus avoiding Belo Horizonte, Minas Gerais, Brazil continuation of the infection to the pathological stage. In [email protected] Chap. 13, A.E. Topolska, L. Wang, C.G. Black, and R.L.