Biology Reference
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(CI) as a method of inducing sterility as an alternative to irradiation. With CI, the release strain of
tsetse would carry a Wolbachia infection that would induce CI when males are mated with wild
females. The competitiveness of these males would be expected to be much higher than irradiated
males and as a result fewer insects would need to be released to achieve the same level of sterility
in the wild population, signiÝcantly reducing the cost of the approach. This strategy depends on the
use of a very efÝcient sexing system. If Wolbachia -infected females are released in sufÝcient
quantities, then Wolbachia would have the opportunity to invade the target population, which would
render subsequent releases ineffective. If it were impossible to guarantee extremely low quantities
of released females, then it would be possible to incorporate low levels of irradiation with Wolbachia -
induced sterility to prevent released females from successfully reproducing.
An alternative control strategy involves replacing the susceptible natural tsetse populations with
their engineered parasite refractory counterparts. However, for the symbiont-based transformation
approach to be successful, a signiÝcant proportion of the natural symbiont population of the gut will
need to be reconstituted by its recombinant counterpart so that foreign expressed products can
accumulate in the gut to levels where they can interfere with trypanosome biology. The eventual
replacement of parasite-susceptible vector populations with engineered refractory Þies could provide
an additional strategy to reduce disease in the Ýeld (Aksoy et al., 2001). If Wolbachia infections in
tsetse do express strong CI phenotypes, the two symbiotic systems could be coupled so as to drive
the phenotypes conferred by the engineered gut-symbionts into the Ýeld. This can be achieved because
as Wolbachia infections rapidly invade populations by virtue of the CI phenomenon they confer, they
can drive other maternally inherited elements, such as mitochondria (Turelli et al., 1992) or the
engineered gut-symbionts, into that same population (Sinkins et al., 1997). While no naturally occur-
ring infectious transfer of Wolbachia has been observed, it has become increasingly common to
experimentally transfer Wolbachia among different hosts and even into insects with no prior infection
history, making it an attractive gene-expression system with a naturally associated driving mechanism
(Boyle et al., 1993; Chang and Wade, 1994; Rousset and de Stordeur, 1994; Poinsot et al., 1998).
The success of symbiont-based transgenic strategies in insects relies on a solid understanding of
the molecular and developmental biology of the symbionts as well as the pathogens transmitted by
each system so that genes with transmission-blocking activities can be identiÝed and efÝciently
expressed in the correct tissues to adversely affect pathogen viability. In addition to questions regarding
technical success and efÝcacy, much current debate focuses on the safety and regulatory concerns for
release of genetically modiÝed insects, especially human-biting vectors. Before any release studies
can be entertained with recombinant animals, information on environmental and ecological hazards
associated with the releases and potential public health risks will need to be deliberated.
ACKNOWLEDGMENTS
Many colleagues have contributed to the development of this body of knowledge in tsetse. I
am grateful to the past and present members of my laboratory for their continued interest and hard
work, in particular Leyla Akman, Xiao-ai Chen, Song Li, Quiying Cheng, Yian Jian, Rita V.M.
Rio, Patricia Strickler, Irene Kasumba, Dana Nayduch, Youjia Hu, and Zhengrong Hao.
REFERENCES
Akman, L. and Aksoy, S. (2001). A novel application of gene arrays: Escherichia coli array provides insight
into the biology of the obligate endosymbiont of tsetse Þies. Proc. Natl. Acad. Sci. U.S.A. 98:
7546Ï7551.
Akman, L., Rio, R.V.M., Beard, C.B., and Aksoy, S. (2001). Genome size determination and coding capacity
of Sodalis glossinidius , an enteric symbiont of tsetse Þies, as revealed by hybridization to Escherichia
coli gene arrays. J. Bacteriol. 183: 4517Ï4525.
 
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