Having completed the genomes of Loa loa, W. bancrofti, and (most recently) O.volvulus, we have utilized the genomic data as the backdrop for performing a large number of proteomic and transcriptomic studies. We have completed a large-scale proteomic and transcriptomic characterization of almost all the major mammalian stages of O. volvulus, resulting in the identification of more than 85-90% of the products predicted from the O. volvulus genome/putative proteome. The analysis also yielded much of the proteome of Wolbachia, the obligate endosymbiont of O. volvulus. Parasite sex- and stage-specific protein expression identified those pathways related to parasite differentiation. To understand better the developmental programs that underscore the transition between the mosquito-derived infective stage larvae (L3) to mammalian adapted L3s and to L4s following a molt, and the initial week of adaptation to the human host, we adapted an in vitro system that allowed for L3 development and subsequent molting to the L4. Using microarray and proteomic assessments at multiple times through this 9 day process we have not only identified those genes/pathways that are critical for the L3/L4 transition but we have also demonstrated by both pharmacologic inhibition (cysteine protease inhibition) and RNAi (of the critical CPLs) the critical role played by cysteine proteases in the early development of mammalian adapted L3s to L4s. We have recently performed shotgun mass spectroscopy on both human sera of patients with defined filarial infections, excretory/secretory (E/S) products of Loa loa microfilariae, all stages of the O. vovlulus worm, and appropriate controls to identify parasite derived biomarkers of active infection. This has led to identification of molecular targets that will be used to configure quantitative immunoassays for the rapid detection of active infection for O. volvulus and Loa loa. Polymorphisms (SNPs) at the entire genome level have been identified for O. volvulus, L. loa and Ascaris lumbricoides. MicroRNA for O. volvulus have been identified in the sera of patients with onchocerciasis and regional differences based on miRNA polymorphisms have been identified.
| Bennuru, Sasisekhar; O'Connell, Elise M; Drame, Papa M et al. (2018) Mining Filarial Genomes for Diagnostic and Therapeutic Targets. Trends Parasitol 34:80-90 |
| O'Connell, Elise M; Kamenyeva, Olena; Lustigman, Sara et al. (2017) Defining the target and the effect of imatinib on the filarial c-Abl homologue. PLoS Negl Trop Dis 11:e0005690 |
| Drame, Papa M; Bennuru, Sasisekhar; Nutman, Thomas B (2017) Discovery of Specific Antigens That Can Predict Microfilarial Intensity in Loa loa Infection. J Clin Microbiol 55:2671-2678 |
| Wang, Jianbin; Gao, Shenghan; Mostovoy, Yulia et al. (2017) Comparative genome analysis of programmed DNA elimination in nematodes. Genome Res 27:2001-2014 |
| Pedram, Bijan; Pasquetto, Valérie; Drame, Papa M et al. (2017) A novel rapid test for detecting antibody responses to Loa loa infections. PLoS Negl Trop Dis 11:e0005741 |
| Bennuru, Sasisekhar; Lustigman, Sara; Abraham, David et al. (2017) Metabolite profiling of infection-associated metabolic markers of onchocerciasis. Mol Biochem Parasitol 215:58-69 |
| Cotton, James A; Bennuru, Sasisekhar; Grote, Alexandra et al. (2016) The genome of Onchocerca volvulus, agent of river blindness. Nat Microbiol 2:16216 |
| O'Connell, Elise M; Nutman, Thomas B (2016) Molecular Diagnostics for Soil-Transmitted Helminths. Am J Trop Med Hyg 95:508-13 |
| Easton, Alice V; Oliveira, Rita G; O'Connell, Elise M et al. (2016) Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming. Parasit Vectors 9:38 |
| Bennuru, Sasisekhar; Cotton, James A; Ribeiro, Jose M C et al. (2016) Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont. MBio 7: |
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