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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZAI1-DDS-M (J2))
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University of Texas Medical Br Galveston
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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

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