Biology Reference
In-Depth Information
Despite extensive study of disease-transmitting arthropods and pathogens, few methods are
available for preventing most vector-borne diseases. Pending development of effective vaccines and
improvement in socioeconomic conditions for the majority of the populations affected by these
diseases, strategies for disease control rely principally on chemical insecticides that eliminate or
reduce numbers of vector insects. Historically, campaigns such as the DDT spraying efforts in the
Indian subcontinent have yielded spectacular short-term results. Several ongoing vector-control
programs, such as the Southern Cone Initiative for control of ChagasÔ disease, have been quite
successful in decreasing transmission of arthropod-borne diseases to humans (SchoÝeld and Dujar-
din, 1997; SchoÝeld and Dias, 1999). However, long-term use of chemical insecticides can be
problematic. Insecticides cause environmental toxicity, and many classes of these chemicals harm
humans. Insects have evolved resistance to many of these agents (World Health Organization, 1992),
and insecticide failure is common. Furthermore, insecticide programs are expensive and difÝcult
to sustain over prolonged periods of time.
TRANSGENIC MODIFICATION
Genetic manipulation of disease-transmitting insects is a potential alternative to strategies aimed
at elimination of vector populations. Expression products of foreign genes that block or eliminate
the ability of the arthropod to transmit pathogens could provide a valuable tool in the control of
several vector-borne diseases. In broad terms, there are two approaches to genetic transformation
of arthropod vectors. The Ýrst involves direct genome transformation via inserted genetic material.
This is accomplished via a variety of mobile elements that are reviewed elsewhere (Coates et al.,
1998; Jasinskiene et al., 1998; Catteruccia et al., 2000). The second approach involves expression
of foreign genes using engineered symbiotic or commensal bacteria that reside within the disease-
transmitting insect. This ÑTrojan HorseÒ method is termed paratransgenesis and will be discussed
in detail in this chapter.
PARATRANSGENESIS
Paratransgenesis is a novel approach to controlling arthropod-borne diseases and is derived from
naturally occurring interactions between vectors, pathogens, and populations of symbiotic or com-
mensal bacteria that reside within the vectors. Many disease-transmitting insects harbor populations
of bacteria that serve important physiologic roles. Obligate blood-sucking insects, such as bed bugs,
sucking lice, and triatomines, employ symbiotic bacteria to provide nutrients that may not be found
in restricted diets. A wide variety of insects harbor specialized bacteria of the genus
Wolbachia
that mediate reproductive Ýtness. Whereas the presence of such microbes within the insect vector
is a foundation for paratransgenic transformation, the following requirements exist for a successful
paratransgenic strategy.
1.
A population of microbes that is amenable to culture and genetic manipulation
in vitro
must exist within a disease-transmitting vector.
2.
Facile methods for isolating and transforming the symbiotic bacteria must be present.
3.
Transformation of the symbiotic bacteria must result in stable mutants, without loss of
reproductive Ýtness of the symbiont.
4.
Genetic manipulation of the bacteria should not affect their symbiotic functions in the
host vector. Paratransgenic vectors that harbor altered symbionts should maintain growth
and reproductive rates comparable to wild-type vectors.
5.
Expression products of the genetically altered bacteria must target pathogens and disrupt
transmission cycles in the host vector. Therefore, localization of transmission-blocking
molecules to appropriate sites of pathogen development is required.
