USA flag logo/image

An Official Website of the United States Government

UV-Based Approach for Accessing New Antibiotics

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / SBIR
Agency Tracking Number:
R43AI096791
Solicitation Year:
2012
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-123
Small Business Information
NovoBiotic Pharmaceuticals, LLC
767C Concord Avenue Cambridge, MA 02138-1044
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2012
Title: UV-Based Approach for Accessing New Antibiotics
Agency: HHS
Contract: 1R43AI096791-01A1
Award Amount: $599,946.00
 

Abstract:

DESCRIPTION (provided by applicant): The goal of this project is to discover novel antibiotics by activating the silent biosynthetic operons of Actinobacteria. Whole genome sequencing of many Actinobacteria showed that there are 10-20 times more operons coding for secondary metabolites than known compounds in a given species. This opens an attractive opportunity to access a large untapped source of new antibiotics. Genetic engineering has been used to turn on silent operons in Actinobacteria, leading to production of secondary metabolites. However, the pace at which engineered operons are activated is very low, less than ten metabolites a year are being reported based on this approach. We reasoned that mutagenesis of isolates that do not produce antimicrobials in vitro will relieve silent operons from regulatory constraints, and screening will then identify the producing mutants. Our preliminary data showed that the approach works surprisingly well, turning over half of the inactive organisms into antibioticproducers. The method is scalable, and we recently identified two potentially novel antimicrobials using this approach. In Phase I, we will mutagenize/screen 2,000 inactive strains for antibiotic production, aiming to obtain new, potentially useful antimicrobials. Biological and chemical dereplication will indicate compounds with potential novelty. We will give priority to broad spectrum compounds with activity against difficult to treat gram-negative pathogens. The antimicrobials will be tested for potency, spectrum, specificity of action and cytotoxicity, and th structure of compounds that pass validation will be determined. Finding 2-3 antimicrobials with novel chemistry will serve as proof-of-principle for this approach. These findings will provide a solid basis for a large-scale drug discovery effort in Phase II. PUBLIC HEALTH RELEVANCE: The overall goal of the project is to develop a simple and efficient method to discover novel antibiotics to combat drug-resistant pathogens that pose a serious health threat in the US and around the world. Novel approaches for discovering antibiotics are desperately needed as the drug pipeline for treating these dangerous human infections continues to diminish.

Principal Investigator:

Losee L. Ling
617-864-2880
lling@novobiotic.com

Business Contact:

Aram Salxman
617-864-2880
asalzman@novobiotic.com
Small Business Information at Submission:

NOVOBIOTIC PHARMACEUTICALS, LLC
767C CONCORD AVE CAMBRIDGE, MA -

EIN/Tax ID: 181063608
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No