Andrew Brittingham, Ph.D.

Carbohydrate utilization and storage by protozoan parasites

Glycogen is a branched polymer of glucose that functions as a store of both energy and carbon skeletons in many species ranging from mammals to bacteria. In collaboration with the laboratory of Dr. Wayne Wilson (Department of Biochemistry and Nutrition) we have begun a study of the role of glycogen stores in the protists Trichomonas vaginalis and Giardia intestinalis. These organisms are both of medical interest. T. vaginalis is the causative agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide where G. intestinalis infection is an important cause of diarrheal illness. Both organisms have been shown to accumulate substantial quantities of glycogen at particular points during growth. Our current work addresses the kinetics of glycogen synthesis and utilization as well as the cellular mechanisms that regulate these processes.

Additionally, we have begun to characterize a family of alpha-amylases present in T. vaginalis. We are particularly interested in determining if alpha-amylases play a role in nutrient acquisition within the glycogen rich environment of the vagina.

The effect of boric acid on Trichomonas vaginalis

Trichomoniasis, caused by Trichomonas vaginalis, is one of the most common non-viral sexually transmitted diseases world-wide, with an estimated 250 million cases occurring annually. In the United States, a single drug class, 5-nitroimidazoles, is currently relied upon in the treatment of trichomoniasis.   There are numerous case reports of infections that are refractory to treatment with nitroimidazoles, and larger studies suggest that low-level metronidazole resistance is present throughout the United States.  Although rare, immediate hypersensitivity reactions to 5-nitroimmmadazoles have also been reported, requiring either patient desensitization or alternative approaches to therapy to be implemented. Recently, intravaginally administered boric acid has been reported to be successful in the treatment of trichomoniasis in cases non-responsive to metronidazole, and in a case of nitroimidazole allergy.  However, the exact mechanism by which boric acid contributes to clinical cure remains unknown.  Work in our lab aims to compare the effectiveness of boric acid to other topical microbicidal agents used in treating T. vaginalis infections.  Additionally we will investigate the mechanisms by which boric acid exerts its microbicidal effect on T. vaginalis.

Publications

Brittingham, A., and Wilson, W.A. 2014. The Antimicrobial Effect of Boric Acid on Trichomonas vaginalis. Sexually Transmitted Diseases 41 (12), 718-722

Dirkx, M., Boyer, M.P., Pradhan, P., Brittingham, A., Wilosn, W.A. 2014. Expression and characterization of a β-fructofuranosidase from the parasitic protist Trichomonas vaginalis. BMC Biochemistry 15: 12-19.

Nielsen T.J., Pradhan P., Brittingham A., Wilson W.A. 2012. Glycogen Accumulation and Degradation by the Trichomonads Trichomonas vaginalis and Trichomonas tenax. Journal of Eukaryotic Microbiology 59(4): 359-366.

Pradhan, P., Lundgren, S.W., Wilson, W.A., and Brittingham, A. 2012. Glycogen Storage and Degradation During in vitro Growth and Differentiation of Giardia intestinalis. Journal of Parasitology 98 (2): 442-444.

Divino, J.N., Chawla, K.S., da Silva, C.M., Bjorge, A.M., and Brittingham, A.  2010. Endothelin-1 production by the canine macrophage cell line DH82: Enhanced production in response to microbial challenge. Veterinary Immunology and Immunopathology 136: 127-132.

Wahl, J.R., Goetsch, N.J., Young, H.J., Van Maanen, R.J., Johnson, J.D., Pea, A.S., and Brittingham, A. 2005. Murine macrophages produce endothelin-1 (ET-1) after microbial stimulation. Experimental Biology and Medicine 230(9): 652-658.

Scolaro, E.J., Ames, R.P., and Brittingham, A. 2005. Growth-phase dependent substrate adhesion in Crithidia fasciculata. The Journal of Eukaryotic Microbiology 52(1): 17-22.

Yao, C., Leidal, K.G., Brittingham, A., Tarr, D.E., Donelson, J.E., and Wilson, M.E. 2002. Biosynthesis of the major surface protease GP63 of Leishmania chagasi. Molecular and Biochemical Parasitology 121(1): 119-28.

Bagentose, L.M., Mentink-Kane, M.M., Brittingham, A., Mosser, D.M., and Monestier, M.  2001. Mercury enhances susceptibility to murine leishmaniasis.  Parasite Immunology 23(12): 633-640. 

Brittingham, A., Miller, M.A., Donelson, J.E., and Wilson, M.E.  2001. Regulation of GP63 mRNA stability in promastigotes of virulent and attenuated Leishmania chagasi. Molecular and Biochemical Parasitology 112(1): 51-59.

Brittingham, A., Chen, G., McGwire, B.S., Chang, K.P., and Mosser, D.M. 1999.  The interaction of Leishmania gp63 with cellular receptors for fibronectin.  Infection and Immunity 67 (9): 4477-4484.

Mosser, D.M. and Brittingham, A. 1997. Leishmania, Macrophages and Complement: A Tale of Subversion and Exploitation. Parasitology 115: S9-S23.

Brittingham, A. and Mosser D.M. 1996. Exploitation of the Complement System by Leishmania Promastigotes. Parasitology Today 12 (11): 444-447. 

Brittingham, A., Morrison, C.J., McMaster, W.R., McGwire, B.S., Chang, K.P., and Mosser D.M. 1995. The Role of the Leishmania Surface Protease, gp63, in Complement Fixation, Cell Adhesion, and Resistance to Complement-Mediated Lysis. The Journal of Immunology 155(6): 3102-3111.

Noel, G.D., Brittingham, A., Granato, A., and Mosser, D.M. 1995.  Effect of Amplification of The Cap B Locus on Complement Mediated Bacteriolysis and Opsonization of Type B Haemophilus influenzae. Infection and Immunity 64 (11): 4769-4775.

Book Chapters

Mosser, D.M. and Brittingham, A. 2002. The interaction of Leishmania spp. with phagocytic receptors on macrophages:  The role of serum opsonins. In Leishmania, J.P. Farrell (ed.) Kluwer Academic Publishers (Boston), World Class Parasites Book Series.