Glickman Lab
Principal Investigator: Michael S Glickman
Institution: Memorial Sloan Kettering Cancer Center (New York, NY)
Primary Subfield: Immunology
Recruitment Status: ✅ Hiring Postdocs
Research Focus
PROJECT SUMMARY Chalkophore mediated respiratory oxidase flexibility and M. tuberculosis virulence Diisonitrile lipopeptides are a novel class of copper-chelating natural products that are biosynthesized by non- ribosomal peptide synthetases found in a variety of Actinobacteria, including Mycobacterium tuberculosis, the bacteria that cause tuberculosis. In multiple studies, genetic disruption of the M. tuberculosis diisonitrile biosynthetic gene cluster attenuates bacterial virulence in mouse models of tuberculosis. This copper-binding activity identifies the diisonitriles as `chalkophores', which are structurally distinct from the well-known methanobactin chalkophores in methanotrophs. Further, we have shown that M. tuberculosis mutants in which chalkophore biosynthesis is disrupted are defective for growth in low-copper or copper-chelated media, and that this defect can be rescued by treatment with exogenous, synthetic diisonitriles, consistent with a role for diisonitriles in copper uptake. We have also shown that the diisonitrile chalkophore system is required to maintain the function of the copper-containing respiratory oxidase in low-copper culture and in mouse infection, est…
Active NIH Awards
- 1R01AI196228-01: Chalkophore mediated respiratory oxidase flexibility and M. tuberculosis virulence (2026)
- 2R01AI064693-20A1: Novel pathway of DNA inter-strand crosslink repair in mycobacteria (2026)
- 1R01CA303125-01A1: Hematopoietic stem cell encoded anti-tumor immunity: mechanisms and function (2026)
- 5R01AI064693-19: Mycobacterial DNA repair and mutagenesis (2024)
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