Towards genetic manipulation of wild mosquito populations to combat malaria: advances and challenges

SUMMARY Malaria kills millions of people every year, yet there has been little progress in controlling this disease. For transmission to occur, the malaria parasite has to complete a complex developmental cycle in the mosquito. The mosquito is therefore a potential weak link in malaria transmission, and generating mosquito populations that are refractory to the parasite is a potential means of controlling the disease. There has been considerable progress over the last decade towards developing the tools for creating a refractory mosquito. Accomplishments include germline transformation of several important mosquito vectors, the completed genomes of the mosquito Anopheles gambiae and the malaria parasite Plasmodium falciparum, and the identification of promoters and effector genes that confer resistance in the mosquito. These tools have provided researchers with the ability to engineer a refractory mosquito vector, but there are fundamental gaps in our knowledge of how to transfer this technology safely and effectively into field populations. This review considers strategies for interfering with Plasmodium development in the mosquito, together with issues related to the transfer of laboratory-acquired knowledge to the field, such as minimization of transgene fitness load to the mosquito, driving genes through populations, avoiding the selection of resistant strains, and how to produce and release populations of males only.

[1]  N. Lobo,et al.  Transposition of the piggyBac element in embryos of Drosophila melanogaster, Aedes aegypti and Trichoplusia ni , 1999, Molecular and General Genetics MGG.

[2]  M. Gossen,et al.  Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  I. Ricci,et al.  Searching for Wolbachia (Rickettsiales: Rickettsiaceae) in Mosquitoes (Diptera: Culicidae): Large Polymerase Chain Reaction Survey and New Identifications , 2002, Journal of medical entomology.

[4]  A. James,et al.  Engineering blood meal-activated systemic immunity in the yellow fever mosquito, Aedes aegypti. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. J. Scott,et al.  A repressible female-specific lethal genetic system for making transgenic insect strains suitable for a sterile-release program. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. James,et al.  Robust gut-specific gene expression in transgenic Aedes aegypti mosquitoes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  C. Curtis.  Possible ways of using transgenic mosquitoes for malaria or dengue control and risk assessment , 2002 .

[8]  D. Kaslow,et al.  A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic as falciparum malaria transmission-blocking vaccines , 1997, Infection and immunity.

[9]  A. James,et al.  Microbe‐induced cytoplasmic incompatibility as a mechanism for introducing transgenes into arthropod populations , 1999, Insect molecular biology.

[10]  D. Thomas,et al.  Insect population control using a dominant, repressible, lethal genetic system. , 2000, Science.

[11]  D. Anxolabéhère,et al.  Molecular characteristics of diverse populations are consistent with the hypothesis of a recent invasion of Drosophila melanogaster by mobile P elements. , 1988, Molecular biology and evolution.

[12]  A. James,et al.  Promoter-directed expression of recombinant fire-fly luciferase in the salivary glands of Hermes-transformed Aedes aegypti. , 1999, Gene.

[13]  D. Hartl,et al.  Regulation of the transposable element mariner , 2004, Genetica.

[14]  F. Catteruccia,et al.  Impact of Genetic Manipulation on the Fitness of Anopheles stephensi Mosquitoes , 2003, Science.

[15]  J. Ribeiro,et al.  A snake venom phospholipase A(2) blocks malaria parasite development in the mosquito midgut by inhibiting ookinete association with the midgut surface. , 2001, The Journal of experimental biology.

[16]  M. Jacobs-Lorena,et al.  Characterization of a carboxypeptidase A gene from the mosquito, Aedes aegypti , 2000, Insect molecular biology.

[17]  R. Ramasamy,et al.  Antibodies to Anopheles midgut reduce vector competence for Plasmodium vivax malaria , 1995, Medical and veterinary entomology.

[18]  S. Meister,et al.  Genome expression analysis of Anopheles gambiae: Responses to injury, bacterial challenge, and malaria infection , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  D. Hartl,et al.  What restricts the activity of mariner-like transposable elements. , 1997, Trends in genetics : TIG.

[20]  Zhicheng Shen,et al.  A type I peritrophic matrix protein from the malaria vector Anopheles gambiae binds to chitin. Cloning, expression, and characterization. , 1998, Journal of Biological Chemistry.

[21]  E. Galun.  Transposable Elements , 2003, Springer Netherlands.

[22]  J. Sacci,et al.  Inhibition of malaria parasite development in mosquitoes by anti-mosquito-midgut antibodies , 1994, Infection and immunity.

[23]  T. Kanda,et al.  Cytogenetics and genetics of vectors. , 1981 .

[24]  C. S. Lofgren,et al.  Genetic method for the preferential elimination of females of anopheles albimanus. , 1978, Science.

[25]  R. Carter,et al.  Transmission-blocking immunity to Plasmodium falciparum in malaria-immune individuals is associated with antibodies to the gamete surface protein Pfs230 , 1999, Parasitology.

[26]  S. Beverley,et al.  cis and trans factors affecting Mos1 mariner evolution and transposition in vitro, and its potential for functional genomics. , 2000, Nucleic acids research.

[27]  C. Beard,et al.  Bacterial symbiosis in arthropods and the control of disease transmission. , 1998, Emerging infectious diseases.

[28]  M. Jacobs-Lorena,et al.  Rapid induction by a blood meal of a carboxypeptidase gene in the gut of the mosquito Anopheles gambiae. , 1997, Insect biochemistry and molecular biology.

[29]  J. Beier,et al.  The midgut bacterial flora of wild Aedes triseriatus, Culex pipiens, and Psorophora columbiae mosquitoes. , 1996, The American journal of tropical medicine and hygiene.

[30]  M. Jacobs-Lorena,et al.  Targeting Plasmodium ligands on mosquito salivary glands and midgut with a phage display peptide library , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[31]  S. Yoshida,et al.  Bacteria expressing single-chain immunotoxin inhibit malaria parasite development in mosquitoes. , 2001, Molecular and biochemical parasitology.

[32]  Xiao-Fan Wang,et al.  Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite , 2002 .

[33]  F. Rousset,et al.  Wolbachia infections are distributed throughout insect somatic and germ line tissues. , 1999, Insect biochemistry and molecular biology.

[34]  H. Bujard,et al.  Tet repressor-based system for regulated gene expression in eukaryotic cells: principles and advances. , 2000, Methods in enzymology.

[35]  Andrea Crisanti,et al.  Stable germline transformation of the malaria mosquito Anopheles stephensi , 2000, Nature.

[36]  C. Beard,et al.  Bacterial symbionts of the triatominae and their potential use in control of Chagas disease transmission. , 2002, Annual review of entomology.

[37]  M. Jacobs-Lorena,et al.  Immunological strategies for control of insect disease vectors: a critical assessment. , 1995, Parasitology today.

[38]  J. Sacci,et al.  Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  M. Turelli,et al.  Rapid spread of an inherited incompatibility factor in California Drosophila , 1991, Nature.

[40]  Christophe Boëte,et al.  Evolutionary ideas about genetically manipulated mosquitoes and malaria control. , 2003, Trends in parasitology.

[41]  T. K. Stevens,et al.  Germline transformation of the malaria vector, Anopheles gambiae, with the piggyBac transposable element , 2001, Insect molecular biology.

[42]  M. G. Kidwell,et al.  Transposable elements as population drive mechanisms: specification of critical parameter values. , 1994, Journal of medical entomology.

[43]  A. James,et al.  Virus-expressed, recombinant single-chain antibody blocks sporozoite infection of salivary glands in Plasmodium gallinaceum-infected Aedes aegypti. , 2000, The American journal of tropical medicine and hygiene.

[44]  E. Walker,et al.  Midgut bacteria in Anopheles gambiae and An. funestus (Diptera: Culicidae) from Kenya and Mali. , 1998, Journal of medical entomology.

[45]  A. Ghosh,et al.  Molecular strategies to study Plasmodium-mosquito interactions. , 2003, Trends in parasitology.

[46]  C. chou,et al.  Is green fluorescent protein toxic to the living cells? , 1999, Biochemical and biophysical research communications.

[47]  W. Engels.  Invasions of P elements. , 1997, Genetics.

[48]  Austin Burt,et al.  Site-specific selfish genes as tools for the control and genetic engineering of natural populations , 2003, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[49]  A. Ghosh,et al.  Bee Venom Phospholipase Inhibits Malaria Parasite Development in Transgenic Mosquitoes* , 2002, The Journal of Biological Chemistry.

[50]  L. Alphey,et al.  Dominant lethality and insect population control. , 2002, Molecular and biochemical parasitology.

[51]  R. Ramasamy,et al.  Effect of anti‐mosquito antibodies on the infectivity of the rodent malaria parasite Plasmodium berghei to Anopheles farauti , 1990, Medical and veterinary entomology.

[52]  R. Carter.  Transmission blocking malaria vaccines. , 2001, Vaccine.

[53]  A. James,et al.  Stable transformation of the yellow fever mosquito, Aedes aegypti, with the Hermes element from the housefly. , 1998, Proceedings of the National Academy of Sciences of the United States of America.