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

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“The discovery, development and deployment of antibiotics have transformed medicine; however, microbes continually evolve and become resistant to these lifesaving drugs,” says NIAID director Anthony S. Fauci, MD. “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, 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 Corporation
 Project Title: Development of Modified R-Type Bacteriocins to Specifically Target Clostridium Difficile and Prevent Relapse of Clostridium Difficile Infections
 Principal Investigator: Gregory Govoni
 Grant: 1 R21AI121692-01

Baylor College of Medicine
 Project Title: Defined Microbial Communities for the Treatment of Recurrent Clostridium Difficile Infection
 Principal Investigator: Robert Britton
 Grant: 1 R21AI121522-01

Project Title: Bacteriophage to Treat Urinary Tract Infections (UTIs) Caused by Multidrug-Resistant Pseudomonas Aeruginosa
 Principal Investigator: Robert Ramig
 Grant: 1 R21AI121545-01

Brigham and Women’s Hospital
 Project Title: Development of the RNA Molecule-Enriched, Cell Type-Specific Exosomes
 Principal Investigator: Yang Jin
 Grant: 1 R21AI121644-01

CUBRC Inc.
 Project Title: Development of HAMLET as an Adjuvant for the Treatment of Drug-Resistant Staphylococcus Aureus Infections
 Principal Investigators: Katie Edwards, Anders Hakansson
 Grant: 1 R21AI121614-01

Emory University
 Project Title: Polymeric Agents for the Treatment of Clostridium Difficile Infections
 Principal Investigators: Shonna McBride, Samuel Gellman
 Grant: 1 R21AI121684-01

Indiana University - Purdue University at Indianapolis
 Project Title: Development of Anti-Virulence Drugs by Targeting the SaeRS Two-Component System of Staphylococcus Aureus
 Principal Investigator: Taeok Bae
 Grant: 1 R21AI121664-01

Massachusetts General Hospital
 Project Title: Synergistic Photodynamic Therapy for Catheter-Associated Urinary Tract Infections (UTIs)
 Principal Investigator: Michael Hamblin
 Grant: 1 R21AI121700-01

Massachusetts Institute of Technology
 Project Title: Engineering “Phagebody” Antimicrobials for Carbapenem-Resistant Enterobacteriaceae
 Principal Investigator: Timothy Lu
 Grant: 1 R21AI121669-01

Medical College of Wisconsin
 Project Title: Bacteriophage to Prevent Infection by Antibiotic-Resistant Enterococci
 Principal Investigator: Christopher Kristich
 Grant: 1 R21AI121552-01

Queen’s University at Kingston
 Project Title: Microbes that Matter: Defining Optimal Formulations for Microbial Ecosystem Therapeutics
 Principal Investigators: Elaine Petrof, Emma Allen-Vercoe
 Grant: 1 R21AI121575-01

The State University of New York at Stony Brook
 Project Title: Small Molecule Inhibition of Pilus Biogenesis by Pathogenic Bacteria
 Principal Investigator: David Thanassi
 Grant: 1 R21AI121639-01

Synthetic Genomics Vaccines, Inc.
 Project Title: Towards the Development of Engineered Phage Therapeutics Against Multidrug-Resistant Pathogens
 Principal Investigator: Bolyn Hubby
 Grant: 1 R21AI121531-01

Texas A&M Agrilife Research
 Project Title: Development of Therapeutic Bacteriophages against Carbapenemase-Resistant Klebsiella Pneumoniae
 Principal Investigators: Jason Gill, Thomas Walsh
 Grant: 1 R21AI121689-01

University of Arizona
 Project Title: A Safe, Targeted, Designer Probiotic to Prevent or Treat Clostridium Difficile Infection
 Principal Investigator: Gayatri Vedantam
 Grant: 1 R21AI121590-01

University of California, San Diego
 Project Title: Nanoparticle Decoys for Treating Infections with Enterotoxin-Producing Pathogens
 Principal Investigators: Lars Eckmann, Liangfang Zhang
 Grant: 1 R21AI121571-01

University of Colorado
 Project Title: Development of Novel Resistance-Modifying Agents for Methicillin-Resistant Staphylococcus Aureus (MRSA)
 Principal Investigator: Xiang Wang
 Grant: 1 R21AI121581-01

Project Title: A Novel Screen for Antibacterials that Are Non-Toxic to Mammals
 Principal Investigators: Corella Detweiler, Xiang Wang
 Grant: 1 R21AI121365-01

University of Texas, Austin
 Project Title: Phage Depolymerases as Antibiotics
 Principal Investigators: James Bull, Ian Molineux
 Grant: 1 R21AI121685-01

University of Texas Health Science Center
 Project Title: Targeting Cell Membrane Adaptation in Multidrug-Resistant Enterococcus Faecium
 Principal Investigator: Cesar Arias
 Grant: 1 R21AI121519-01

University of Texas Medical Branch
 Project Title: Therapeutic Potential of Cystatin 9 Treatment to Fight Bacterial Pneumonia
 Principal Investigator: Tonyia Eaves-Pyles
 Grant: 1 R21AI121604-01   

University of Sydney
 Project Title: Harnessing Bacteriophages as Natural Predators to Combat the Superbugs: A Pulmonary Drug Delivery Approach
 Principal Investigator: Kim Chan
 Grant: 1 R21AI121627-01   

University of Wisconsin-Madison
 Project Title: Microbial-Ecology Guided Discovery of Non-Traditional Therapeutics that Limit Resistance
 Principal Investigator: Jason Kwan
 Grant: 1 R21AI121704-01

Project Title: A Biotherapeutic CRISPR-Delivery Platform to Eradicate Clostridium Difficile
 Principal Investigator: Jan-Peter van Pijkeren
 Grant: 1 R21AI121662-01