Cyclopropane Modification of Trehalose Dimycolate Drives Granuloma Angiogenesis and Mycobacterial Growth through Vegf Signaling

• Published in: Cell host & microbe Vol. 24; no. 4; pp. 514 - 525.e6
• Main Authors: Walton, Eric M., Cronan, Mark R., Cambier, C.J., Rossi, Andrea, Marass, Michele, Foglia, Matthew D., Brewer, W. Jared, Poss, Kenneth D., Stainier, Didier Y.R., Bertozzi, Carolyn R., Tobin, David M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.10.2018
• Subjects: angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cord Factors - metabolism; Disease Models, Animal; granuloma; host-directed therapy; Humans; Indazoles; macrophage; Macrophages - immunology; Macrophages - microbiology; Methyltransferases - genetics; Methyltransferases - metabolism; Mycobacterium Infections, Nontuberculous - immunology; Mycobacterium Infections, Nontuberculous - microbiology; Mycobacterium marinum - enzymology; Mycobacterium marinum - genetics; Mycobacterium marinum - pathogenicity; Mycolic Acids - metabolism; Neovascularization, Pathologic - immunology; Neovascularization, Pathologic - microbiology; Neovascularization, Pathologic - pathology; PcaA; Pyrimidines - pharmacology; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors; Receptors, Vascular Endothelial Growth Factor - drug effects; Receptors, Vascular Endothelial Growth Factor - metabolism; Signal Transduction; Sulfonamides - pharmacology; trehalose dimycolate; Tuberculoma - immunology; Tuberculoma - microbiology; Tuberculoma - pathology; tuberculosis; vegf; Zebrafish; angiogenesis; PcaA; tuberculosis; granuloma; vegf; macrophage; host-directed therapy; zebrafish; trehalose dimycolate

Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. As granuloma angiogenesis favors the infecting mycobacteria, it may be actively promoted by bacterial determinants during infect...