Methods and Compositions for Anti-Virulence Therapeutics

Principal Investigators: Nicholas Oberlies, Jose Alberto Chavez, Huzefa Raja, Nadja Cech, Justin Stempin

Application Number: 62/831,990

UNCG Innovation: 19-0005

Category: Chemistry & Biochemistry

Current treatment options for bacterial infections are dependent on antibiotics that inhibit microbial growth and viability. These approaches result in the evolution of drug resistant strains of bacteria. An anti-infective strategy that is less likely to lead to the development of resistance is the disruption of quorum sensing mechanisms, which are involved in promoting virulence. The goal of this study was to identify fungal metabolites effective as quorum sensing inhibitors. Three new prenylated xanthenes (1-3), along with two
known compounds, 4R-regiolone (4) and decarboxycitrinone (5), were isolated from a freshwater fungus from North Carolina (Leotiomycetes sp.). Their structures were assigned on the basis ofHRESIMS and NMR experiments. The structure of compound 1 was confinned via x-ray diffraction analysis, and its
absolute configuration was established by TDDFT-ECD calculations. Compounds 1-3 suppressed quorum sensing in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), with ICso values ranging
from 0.3 to 12.5 µM. These compounds represent potential leads in the development of anti-virulence therapeutics.

Immediate & Future Applications:
The idea of treating ‘infection’ with anti-virulence compounds could have application in any scenario where there is a wound. This could be wounds from the environment (scrapes), combat (knives, gunshot, etc.), or comorbidity (diabetes). In any scenario where there is an infection, a compound that will help the ‘host’ clear the infection could have value.

Inventor info: Nicholas Oberlies

Inventor Info: Noemi Paguigan

Inventor Info: Jose Alberto Chavez

Inventor Info: Huzefa Raja

Inventor Info: Nadja Cech

Inventor Info: Justin Stempin