The autophagic delivery of intracellular pathogens to the lysosome (where they are destroyed) is emerging as a central mechanism of innate immunity; accordingly, the augmentation of host autophagy represents a potentially powerful new therapeutic approach to combat intracellular pathogens1-3. In our original project, we pursued four specific aims to develop an autophagy-inducing peptide that may be useful as a novel therapeutic in the treatment of diverse intracellular NIAID Class A, B, and C Priority pathogens.
These aims i ncluded: 1. To confirm that the Tat-Beclin 1 peptide is a specific inducer of autophagy in vitro and in vivo. 2. To evaluate the mechanism by which the Tat-Beclin 1 induces autophagy. 3. To evaluate the effects of the Tat-Beclin 1 peptide on the in vitro growth of selected NIAID Category A, B, and C Priority Pathogens. 4. To evaluate the effects of the Tat-Beclin 1 peptide on microbial pathogenesis in mouse models of infection with selected NIAID Category A, B, and C Priority Pathogens. Thus far, we have completed the first aim and made significant progress towards completing Aims 2-4. To accelerate the development of a novel broad-spectrum antimicrobial biological product, the Tat-Beclin 1 autophagy-inducing peptide, we propose to work further on Aims 2-4 in parallel with investigations to determine the optimal dosing, immunogenicity, and preliminary safety profile of the peptide. These studies will help advance the development of a biologically active peptide (or small molecule compound that mimics its action) for the treatment of NIAID priority intracellular pathogens.
|Paterson, Andrew S; Raja, Balakrishnan; Mandadi, Vinay et al. (2017) A low-cost smartphone-based platform for highly sensitive point-of-care testing with persistent luminescent phosphors. Lab Chip 17:1051-1059|
|Raja, B; Goux, H J; Marapadaga, A et al. (2017) Development of a panel of recombinase polymerase amplification assays for detection of common bacterial urinary tract infection pathogens. J Appl Microbiol 123:544-555|
|Nunes, Marcio R T; Contreras-Gutierrez, María Angélica; Guzman, Hilda et al. (2017) Genetic characterization, molecular epidemiology, and phylogenetic relationships of insect-specific viruses in the taxon Negevirus. Virology 504:152-167|
|Rossetti, Carlos A; Drake, Kenneth L; Lawhon, Sara D et al. (2017) Systems Biology Analysis of Temporal In vivo Brucella melitensis and Bovine Transcriptomes Predicts host:Pathogen Protein-Protein Interactions. Front Microbiol 8:1275|
|Aghazadeh, Amirali; Lin, Adam Y; Sheikh, Mona A et al. (2016) Universal microbial diagnostics using random DNA probes. Sci Adv 2:e1600025|
|Park, Arnold; Yun, Tatyana; Hill, Terence E et al. (2016) Optimized P2A for reporter gene insertion into Nipah virus results in efficient ribosomal skipping and wild-type lethality. J Gen Virol 97:839-43|
|Inglis, Fiona M; Lee, Kim M; Chiu, Kevin B et al. (2016) Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation. J Neurovirol 22:140-8|
|Case, Elizabeth Di Russo; Smith, Judith A; Ficht, Thomas A et al. (2016) Space: A Final Frontier for Vacuolar Pathogens. Traffic 17:461-74|
|Galaz-Montoya, Jesús G; Hecksel, Corey W; Baldwin, Philip R et al. (2016) Alignment algorithms and per-particle CTF correction for single particle cryo-electron tomography. J Struct Biol 194:383-94|
|Raja, Balakrishnan; Pascente, Carmen; Knoop, Jennifer et al. (2016) An embedded microretroreflector-based microfluidic immunoassay platform. Lab Chip 16:1625-35|
Showing the most recent 10 out of 377 publications