Chagas disease afflicts over 12 million people in Central and South America. Eradication efforts directed at the triatomine vectors of this disease have been effective, but are fraught with issues of cost, toxicity of pesticides and vector resistance. A paratransgenic strategy is being developed as an adjunctive approach. Rhodococcus rhodnii, the symbiont of Rhodnius prolixus, has been transformed to express cecropin A, an anti-trypanosomal peptide. Parasite-refractory R. prolixus have been developed in the lab and a single chain antibody has been expressed in these insects. Strategies for spreading transgenic symbionts into field vectors and detailed risk assessment are under development. Field use will require an armamentarium of molecules that target multiple sites on T. cruzi. This 4 year application aims to develop 3 broad classes of molecules with anti- trypanosomal activity. The first of these, addressed in Aim 1, are single chain antibodies (scFv). The surface glycoprotein, gp72, an integral part of T. cruzi maturation, is the first target for scFv development.
In Aim 2, immune peptides related to cecropin A- magainin, moricin, mellitin and Apidaecin will be tested for activity against T. cruzi.
In Aim 3, mannosidase and lyticase that target the surface sugar moieties of T. cruzi will be developed as effector molecules. cDNA of all classes of molecules will be expressed in the bacterium R. rhodnii to assess selective toxicity to T. cruzi and effects on bacterial physiology.
In Aim 4, potential toxicity of transgenic R. rhodnii to R. prolixus will be determined. Furthermore, strategies to deliver combinations of transgenic bacteria concurrently will be explored. This project aims to develop multiple lines of transgenic bacteria expressing anti- trypanosomal molecules, to be used for future field deployment in the ongoing battle against Chagas disease. The Rhodnius prolixus system will potentially have application in a defined geographical area but will also serve as a model for paratransgenic control of Chagas disease, in other endemic regions, with other triatomine vectors of Chagas disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Vector Biology Study Section (VB)
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Costero, Adriana
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University of New Mexico
Internal Medicine/Medicine
Schools of Medicine
United States
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Jose, Christo; Klein, Nicole; Wyss, Sarah et al. (2013) Recombinant Arthrobacter ?-1, 3-glucanase as a potential effector molecule for paratransgenic control of Chagas disease. Parasit Vectors 6:65
Hurwitz, Ivy; Fieck, Annabeth; Durvasula, Ravi (2012) Antimicrobial peptide delivery strategies: use of recombinant antimicrobial peptides in paratransgenic control systems. Curr Drug Targets 13:1173-80
Markiv, Anatoliy; Anani, Bernard; Durvasula, Ravi V et al. (2011) Module based antibody engineering: a novel synthetic REDantibody. J Immunol Methods 364:40-9
Markiv, Anatoliy; Beatson, Richard; Burchell, Joy et al. (2011) Expression of recombinant multi-coloured fluorescent antibodies in gor -/trxB- E. coli cytoplasm. BMC Biotechnol 11:117
Hurwitz, Ivy; Fieck, Annabeth; Read, Amber et al. (2011) Paratransgenic control of vector borne diseases. Int J Biol Sci 7:1334-44
Fieck, Annabeth; Hurwitz, Ivy; Kang, Angray S et al. (2010) Trypanosoma cruzi: synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts. Exp Parasitol 125:342-7
Pinto, C Miguel; Baxter, B Dnate; Hanson, J Delton et al. (2010) Using museum collections to detect pathogens. Emerg Infect Dis 16:356-7
Durvasula, Ravi V; Sundaram, Ranjini K; Kirsch, Philipp et al. (2008) Genetic transformation of a Corynebacterial symbiont from the Chagas disease vector Triatoma infestans. Exp Parasitol 119:94-8