SYRINGOLINS AS INHIBITORS OF THE MYCOBATERIAL PROTEASOME

SYRINGOLINS AS INHIBITORS OF THE MYCOBACTERIAL PROTEASOME

Researchers at UCSF have discovered a novel prospective compound for the treatment of tuberculosis.

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis (Mtb) and is one of the deadliest infectious diseases worldwide. As more strains become resistant to existing drugs, it’s expected that tuberculosis cases will become harder to treat, increasing the need for new medications. Scientists have found that the bacterium relies on a structure called the 20S proteasome to survive, especially under stressful conditions inside the human body. However, targeting this structure is difficult because similar systems exist in human cells, so treatments must specifically affect the bacteria without harming the patient. Overall, there is a strong need to develop new drugs that can safely and effectively kill the tuberculosis bacterium.

Stage of Research

This invention comprises a novel therapeutic treatment for Mtb. Specifically, the inventors have discovered that syringolins and syringolin-like compounds are successful in inhibiting Mtb, the causative bacterium for tuberculosis in humans. Syringolins are small peptide-like molecules with a reactive group that allows it to bind irreversibly to the proteasome. This in turn blocks the proteasome which is the cell’s protein “recycling” system and is a key part of protein degradation and quality control. Studies in cell cultures have shown that syringolins can also enhance the efficacy of known Mtb treatments such as pretomanid.

Applications

• Treatment of tuberculosis in humans

Advantages

• Can inhibit Mtb when used alone or in conjunction with known Mtb treatments such as pretomanid
• Not currently widely used compounds, so little risk of Mtb drug resistance

Stage of Development

Research- in vitro

Technology Reference

CZ Biohub ref. no. CZB-338F

UCSF ref. no. SF-2025-196

Keywords

Infectious disease, bacteria, therapeutic