Drug-induced alterations in gene expression of the asexual blood forms of Plasmodium falciparum

摘要: The complete genome sequence of the malarial parasite, Plasmodium falciparum [Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., and Hyman, R.W. (2002) Nature 419: 498-510; R.W., Conway, A., Kurdi, Mao, J., Miranda, M. et al. 534-537], has provided researchers with informational base for establishing genomic [Volkman, S.K., Hartl, D.L., Wirth, D.F., Nielsen, K.M., Choi, Batalov, S., Science 298: 216-218], proteomic [Florens, L., Washburn, M.P.J.D.R., Anthony, R.M., Grainger, Haynes, J.D., 520-526; Lasonder, Ishihama, Y., Anderson, J.S., Vermunt, A.M.W., Pain, Sauerwein, 537-542] genome-wide RNA expression [Ben Mamoun, C., Gluzman, I.Y., Hott, MacMillan, Amarakone, A.S., (2001) Mol Microbiol 39: 26-36; Hayward, R.E., Derisi, J.L., Alfadhli, Kaslow, D.C., Brown, P.O., Rathod, P.K. (2000) 35: 6-14] analyses in this system. In fact, we have previously utilized SAGE (serial analysis gene expression) to identify abundant loci that probably constitute part active metabolome [Patankar, Munasinghe, Shoaibi, Cummings, L.M., D.F. Biol Cell 12: 3114-3125], as well characterize antisense transcription on a global scale Plasmodium. present study, comprehensive annotation libraries derived from an asexual stage population exposed drug its matched control was used assess modulation by chloroquine. Here, observed constellation changes, differential regulation over 100 transcripts, confirmed data alternate methods. A few responsive loci, including PfMDR1, been implicated mechanism chloroquine action/resistance. Several others, however, were unexpected categories, large number unknown open reading frames (ORFs), whose induction after exposure may provide first hints their possible function.