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A Novel Therapeutic Agent for the Treatment of Gram-positive Infections

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI149803-01A1
Agency Tracking Number: R41AI149803
Amount: $233,066.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA19-270
Timeline
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-08-13
Award End Date (Contract End Date): 2021-07-31
Small Business Information
606 COACHLIGHT CT
College Station, TX 77845-8145
United States
DUNS: 078514829
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 JAMES SMITH
 (855) 384-7266
 jsmith@sanochemicals.com
Business Contact
 JAMES SMITH
Phone: (855) 384-7266
Email: james.smith@sanochemicals.com
Research Institution
 TEXAS A&M UNIVERSITY
 
400 HARVEY MITCHELL PARKWAY SOUTH
COLLEGE STATION, TX 77845-4375
United States

 Nonprofit College or University
Abstract

Project Summary
The work described in the application is necessary for furthering the development of a new
therapeutic for treating Gram-positive infections. Preliminary in vitro and in vivo activity studies of
novel analogs of mutacin 1140 suggest that they hold great promise as an antimicrobial product
for clinical use. Mutacin 1140 is produced by the bacterium Streptococcus mutans JH1140 and
the bacterium has been engineered to synthesize novel analogs of the native compound. Our
studies have revealed that select mutacin 1140 analogs have a rapid bactericidal activity and that
they are superior to native compound in terms of inhibitory activity, serum stability, and
performance in an in vivo infection study. Further, the analogs have been shown to be more
effective than vancomycin in treating a systemic MRSA infection. Mutacin 1140 analogs have no
observable toxicity in mice at a 50 mg/kg intravenous dose. Furthermore, the analogs were shown
to significantly reduce bacterial load of MRSA in the kidneys and liver of infected mice in an acute
infection study. All these studies point to the need to further the preclinical development of one or
more of the novel analogs of mutacin 1140. The major impediment to furthering investigational
studies on these unique antibacterial compounds is the poor yield from culture liquor. The goal of
this application is to enhance the yield and purity of mutacin analogs following fermentation. Three
approaches will be explored to increase the yield of the antibacterial compound. First, media
components will be screened to determine their effect on the production levels of the antibacterial
compound. Second, a molecular based approach will be used to determine whether an increase
in production of the analogs is possible through genetic manipulation of S. mutans. Our third
approach is transposon or ethyl-methanesulfonate (EMS) random mutagenesis coupled with
next-generation DNA sequencing to identify mutations that lead to enhanced production. The last
component of the application is to determine the most effective means of extracting and purifying
the antibacterial compound from the fermentation liquor. These experiments will enable
exploratory studies for defining a novel drug product for investigational new drug (IND) studies.Project Narrative
The proposal addresses the need for the development of novel treatments for Gram-
positive infections. We will investigate means of enhancing the production and
purification of lead analogs of the antibacterial compound mutacin 1140. This work is
necessary for promoting the production of sufficient amounts of the analogs for the
completion of the required preclinical studies that are needed for filing an Investigational
New Drug (IND) application.

* Information listed above is at the time of submission. *

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