M. Arai et al., Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate gametogenesis of Plasmodium in the midgut of the mosquito, MOL BIOCH P, 116(1), 2001, pp. 17-24
Gametogenesis of Plasmodium in vitro can be induced by the combined stimulu
s of a 5 degreesC fall in temperature and the presence of xanthurenic acid
(XA). In vitro experiments showed that P. gallinaceum (EC50 = 80 nM) is muc
h more sensitive to XA than P. berghei (9 muM), P. yoelii (8 muM), and P. f
alciparum (2 muM). However, in the mosquito vector, we do not know whether
the temperature shift and XA are the only gametocyte-activating factors (GA
F), nor do we know with certainty the true source(s) of XA in the mosquito
blood meal. Previous studies indicate that XA is the only source of GAF in
the mosquito. By defining, and then contrasting, the ability of an XA-defic
ient mutant of Aedes aegypti, with the wild-type mosquito to support exflag
ellation and ookinete formation in vivo, we determined the roles of parasit
e-, mosquito- and host blood-derived GAF in the regulation of gametogenesis
of P. gallinaceum. Removal of both host and vector sources of GAF totally
inhibited both exflagellation and ookinete production, whilst the lack of e
ither single source resulted in only a partial reduction of exflagellation
and ookinete formation in the mosquito gut. Both sources can be effectively
replaced/substituted by synthetic XA. This suggests (1) both mosquito- and
vertebrate-derived factors act as GAF in the mosquito gut in vivo; (2) the
parasite itself is unable to produce any significant GAF activity. Studies
are underway to determine whether vertebrate-derived GAF is XA. These data
may form the basis of further studies of the development of new methods of
interrupting malarial transmission. (C) 2001 Elsevier Science B.V. All rig
hts reserved.