Compositions and methods for treating microbial infections

US10045966B2 · kind B2 · utility

Assignee

• VANDERBILT UNIVERSITY · US

Inventors

• Eric P. Skaar · Brentwood, US
• Laura Anzaldi Mike · Nashville, US
• Gary A. Sulikowski · Brentwood, US
• Alex G. Waterson · Durham, US
• Paul R. Reid · Durham, US

Key dates

• Filing date: Apr 21, 2017
• Grant date: Aug 14, 2018
• Expiry date: Apr 21, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q1/18
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Embodiments of the presently-disclosed subject matter include activators of HssRS that induce endogenous heme biosynthesis by perturbing central metabolism. These molecules are toxic to fermenting S. aureus, including clinically relevant small colony variants (SCVs). The utility of targeting fermenting bacteria is exemplified by the fact that this compound prevents the emergence of antibiotic resistance, enhances phagocyte killing, and reduces S. aureus pathogenesis. This small molecule is a powerful tool not only for studying bacterial heme biosynthesis and central metabolism, but also establishes targeting of fermentation as a viable antibacterial strategy.