METABOLIC ALDEHYDES AS IMMUNE EFFECTORS AGAINST TUBERCULOSIS

This proposal will continue to test the hypothesis that host-derived aldehydes are a critical component of host immunity against Mycobacterium tuberculosis. In the past funding period, we used bacterial and mouse genetics, biochemistry, immunology and cell biology experiments to test this hypothesis. We have identified bacterial mutants that are more sensitive than parental strains to various aldehydes. We have shown that these mutants are attenuated in mice with defects in aldehyde detoxification, showing that host-derived aldehydes can contribute to bacterial control. We continue to characterize the bacterial and host pathways. We are now working with TB Alliance to test frontline TB drugs on mice defective for aldehyde detoxification to determine if repurposing an FDA-approved drug that inhibits ALDH2 could improve TB treatment.