NIH awards will support development of therapeutic alternatives to traditional antibiotics

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has awarded approximately $5 million in funding for 24 research projects seeking to develop non-traditional therapeutics for bacterial infections to help address the growing health threat of antibiotic resistance. Advancing new therapeutic options to combat drug-resistant bacteria is a key goal of the President's National Action Plan for Combating Antibiotic-Resistant Bacteria.

"The discovery, development and deployment of antibiotics have transformed medicine; however, microbes continually evolve and become resistant to these lifesaving drugs," said NIAID Director Anthony S. Fauci, M.D. "New strategies are desperately needed to treat patients with antibiotic-resistant infections that often are deadly. These new NIAID grants will provide funding to researchers developing unique, non-traditional therapies that could complement or even replace currently available antibiotics that are losing effectiveness."

Increasing resistance to antibiotics coupled with the slow pace of new antibiotic development threatens to erode the past 70 years of progress in fighting life-threatening bacterial infections. The overuse and abuse of antibiotics drives this issue and, as a consequence, bacteria adapt to antibiotics designed to destroy them, making the drugs less effective and allowing antibiotic-resistant strains to survive and multiply.

A non-traditional therapeutic is an antibacterial treatment that works differently than traditional antibiotics, which typically target one or more essential pathways, such as those involved in cell-wall and protein synthesis, to directly kill or inhibit the growth of many types of bacteria. One non-traditional approach, called therapeutic bacteria, uses good bacteria found in or added to the human microbiome to target or control the growth of harmful bacteria. Another alternative approach is bacteriophage or phage therapy, which uses viruses that only affect bacteria to reduce or eliminate those bacteria in humans. Other examples of non-traditional approaches include adding decoy targets to prevent bacterial pathogens from producing disease, enhancing human immune responses to pathogens, and developing drugs that incapacitate the pathogen's ability to adapt and compete. For more information on NIAID's research in this area, please see the recent report NIAID's Antibacterial Resistance Program: Current Status and Future Directions.

The 24 phased innovation awards were made to 18 academic institutions and three industrial organizations. The awards provide support for two years with the possibility of three additional years of funding for the most accomplished projects. The recipients are as follows:

Avidbiotics CorporationProject Title: Development of Modified R-Type Bacteriocins to Specifically Target Clostridium Difficile and Prevent Relapse of Clostridium Difficile InfectionsPrincipal Investigator: Gregory GovoniGrant: 1 R21AI121692-01

Baylor College of MedicineProject Title: Defined Microbial Communities for the Treatment of Recurrent Clostridium Difficile InfectionPrincipal Investigator: Robert BrittonGrant: 1 R21AI121522-01Project Title: Bacteriophage to Treat Urinary Tract Infections (UTIs) Caused by Multidrug-Resistant Pseudomonas AeruginosaPrincipal Investigator: Robert RamigGrant: 1 R21AI121545-01Brigham and Women's HospitalProject Title: Development of the RNA Molecule-Enriched, Cell Type-Specific ExosomesPrincipal Investigator: Yang JinGrant: 1 R21AI121644-01CUBRC Inc.Project Title: Development of HAMLET as an Adjuvant for the Treatment of Drug-Resistant Staphylococcus Aureus InfectionsPrincipal Investigators: Katie Edwards, Anders HakanssonGrant: 1 R21AI121614-01Emory UniversityProject Title: Polymeric Agents for the Treatment of Clostridium Difficile InfectionsPrincipal Investigators: Shonna McBride, Samuel GellmanGrant: 1 R21AI121684-01Indiana University—Purdue University at IndianapolisProject Title: Development of Anti-Virulence Drugs by Targeting the SaeRS Two-Component System of Staphylococcus AureusPrincipal Investigator: Taeok BaeGrant: 1 R21AI121664-01Massachusetts General HospitalProject Title: Synergistic Photodynamic Therapy for Catheter-Associated Urinary Tract Infections (UTIs)Principal Investigator: Michael HamblinGrant: 1 R21AI121700-01Massachusetts Institute of TechnologyProject Title: Engineering "Phagebody" Antimicrobials for Carbapenem-Resistant EnterobacteriaceaePrincipal Investigator: Timothy LuGrant: 1 R21AI121669-01Medical College of WisconsinProject Title: Bacteriophage to Prevent Infection by Antibiotic-Resistant EnterococciPrincipal Investigator: Christopher KristichGrant: 1 R21AI121552-01Queen's University at KingstonProject Title: Microbes that Matter: Defining Optimal Formulations for Microbial Ecosystem TherapeuticsPrincipal Investigators: Elaine Petrof, Emma Allen-VercoeGrant: 1 R21AI121575-01The State University of New York at Stony BrookProject Title: Small Molecule Inhibition of Pilus Biogenesis by Pathogenic BacteriaPrincipal Investigator: David ThanassiGrant: 1 R21AI121639-01Synthetic Genomics Vaccines, Inc.Project Title: Towards the Development of Engineered Phage Therapeutics Against Multidrug-Resistant PathogensPrincipal Investigator: Bolyn HubbyGrant: 1 R21AI121531-01Texas A&M Agrilife ResearchProject Title: Development of Therapeutic Bacteriophages against Carbapenemase-Resistant Klebsiella PneumoniaePrincipal Investigators: Jason Gill, Thomas WalshGrant: 1 R21AI121689-01University of ArizonaProject Title: A Safe, Targeted, Designer Probiotic to Prevent or Treat Clostridium Difficile InfectionPrincipal Investigator: Gayatri VedantamGrant: 1 R21AI121590-01University of California, San Diego Project Title: Nanoparticle Decoys for Treating Infections with Enterotoxin-Producing PathogensPrincipal Investigators: Lars Eckmann, Liangfang ZhangGrant: 1 R21AI121571-01University of ColoradoProject Title: Development of Novel Resistance-Modifying Agents for Methicillin-Resistant Staphylococcus Aureus (MRSA)Principal Investigator: Xiang WangGrant: 1 R21AI121581-01Project Title: A Novel Screen for Antibacterials that Are Non-Toxic to MammalsPrincipal Investigators: Corella Detweiler, Xiang WangGrant: 1 R21AI121365-01University of Texas, AustinProject Title: Phage Depolymerases as AntibioticsPrincipal Investigators: James Bull, Ian MolineuxGrant: 1 R21AI121685-01University of Texas Health Science CenterProject Title: Targeting Cell Membrane Adaptation in Multidrug-Resistant Enterococcus FaeciumPrincipal Investigator: Cesar AriasGrant: 1 R21AI121519-01University of Texas Medical BranchProject Title: Therapeutic Potential of Cystatin 9 Treatment to Fight Bacterial PneumoniaPrincipal Investigator: Tonyia Eaves-PylesGrant: 1 R21AI121604-01University of SydneyProject Title: Harnessing Bacteriophages as Natural Predators to Combat the Superbugs: A Pulmonary Drug Delivery ApproachPrincipal Investigator: Kim ChanGrant: 1 R21AI121627-01 University of Wisconsin-MadisonProject Title: Microbial-Ecology Guided Discovery of Non-Traditional Therapeutics that Limit ResistancePrincipal Investigator: Jason KwanGrant: 1 R21AI121704-01Project Title: A Biotherapeutic CRISPR-Delivery Platform to Eradicate Clostridium DifficilePrincipal Investigator: Jan-Peter van PijkerenGrant: 1 R21AI121662-01

Provided by NIH/National Institute of Allergy and Infectious Diseases