JL1 Plasmodium-Anopheles intimacy : From Ross to the 21st century

2001 Medical Entomology and Zoology  
The JapanSociety of Medical Entomology and Zoology fim:ii ÷ fi.A=ptsst ' fiMngsui}Hpt I G・MtsXU-as-,Hfi11 ptft : gmee= (gem) ptft : fi#eex (]scwa ± ) JLI plasmodium -Anopheles intimacy: From Ross to the 21st century OBREY PAUL T. ' When Ronald Ross discovered the sporogonic cycle of Plasmodium in mosquitoes in 1897 he predicted that it would relatively easy to control malaria through vector control arrd with chemotherapeutic agents, such as quinine, We know today that Ross seriously
more » ... riously underestimated the capacity ef the parasite-vector tandem to surmount man's efforts to interrupt transmission, Bloodsucking insects appeared on earth during the Cretaceous period (140-65 Ma) feeding on saurian reptiles and primitive amphibians and most certainly transmitting their hematozoonan parasites long before humanoids evolved, This long co-evolution has provide both parasite and invertebrate host an intimate knowledge of each other in order to deal will each other's presence. This is especially true for Plasmodit.{m that relies on a mQsquito as its primary host and vector, as well as a vertebrate host as its repository to amplify its asexual forms and sexual precursor cells that infect the mosquito, To move from mosquito to vertebrate host is a seemingly daunting task for the parasite that requires fine tuned signaling to orient itself temporally anq, spatially to ensure successfu1 transmissien. ,Scientists have tried to fathom the mosquito-Plasmodium relationship and have been partially successfu1 in certain areas, but have failed to grasp sufficient information to make any real impact on disease transmission. To take this understanding of the host-parasite re!ationship to another level, unveiling of the parasite's and host's genome sequences will be necessaTy to provide novel malaria control strategies for the 2IS'century・ JL2 Evidence that mutations in the Plasmodium folciparum digestive vacuole transmembrane The increasing failure of chlorequine (CQ) against malaria has produced seyere public health setbacks in recent years, especially ameng pediatTic populations of sub-Saharan Aflica. No alternative dmg is now available with the affordability, low toxicity, and efficacy that once characterized CQ. Thc requirement for new dmgs that can rep]ace or reviye CQ emphasizes the need to unclerstand the action of CQ and the mechanisrn by which resistant P. falcipanim parasites counter its effects. In this talk I will describe collaborative werk on P. falcipar"m CQ resistance (CQR) from research groups at the this work, we used a genetic cross between CQR and CQ sensitiye (CQS) parasite clones to map the determinant of resistance within a 36-kb region ef chremosome 7. This region was eventually shown to harbor a 13 exon gene, lti? rt, having mutations that completely associate with the in vitro CQR phenotype of parasites from Southeast Asia, Afuca and South Arr}erica, Whereas the CQR phenotype could not be altercd by allelic medifications of candidate genes initially describecl from the 36 kb regien (cgl, cg2), verupami1-reyersible CQR was detected after genetic transformation of CQS parasites with mutant ntl rt constructs. The encoded PfCRT molecule is a transmembrane molecule that lecalizes to the parasite digestive vacuole and is probably rcspensible for a critical transporter function. The mutations Tnay result in altered CQ flux at the digestive vacuole membrane or in reduced CQ binding to hematin through an effect on digestive vacuole pH, PfCRT mutations haye been evaluatcd in field studies. Results show that PfCRT mutation T76 may servc as a useful marker for the surveMance of CQR falciparum malaria. i/ ho xt -71-NII-Electronic
doi:10.7601/mez.52.71_1 fatcat:mci4deyj3navtaugpncpukqfsm