Taking Aim at TB’s Nutrient Acquisition

Tuberculosis, a disease caused by the bacteria Mycobacterium tuberculosis (Mtb), is responsible for approximately 1.6 million deaths worldwide every year. A key facet of tuberculosis is Mtb’s ability to take fatty acids, cholesterols, and other lipids from its host. Mtb transports these lipids through its cellular membrane and metabolizes them to sustain itself and to promote disease.

To move host-derived lipids through its cellular membrane, Mtb relies on a complex system of biochemical signals and protein interactions. Brian C. VanderVen, Microbiology and Immunology, is identifying operative proteins in Mtb’s lipid transport system and characterizing how they function. VanderVen’s first aim is to determine with what specificity lipid transporters target particular lipid substrates. The substrate acts as a molecular handle that allows the transporter to identify the lipid and engage with it. Preliminary work by the VanderVen lab suggests that certain transporters may target fatty acids that human cells need to build immune-signaling lipids; hence, a second aim is to evaluate whether, by scavenging these fatty acids, Mtb alters the host’s immune responses to infection. A third aim is to identify proteins that Mtb must produce to keep its lipid transport system functioning. By silencing the genes in Mtb that generate those key multifunctional proteins, VanderVen’s lab will assess whether drugs that block those proteins might be effective against tuberculosis.

This research will detail the biochemical mechanisms by which Mtb acquires host-derived nutrients. By determining whether these pathways have therapeutic potential, this research could generate new strategies and drug targets for fighting tuberculosis.

NIH Award Number: 1R01AI150916-01

Cornell Researchers

Funding Received

$2.9 Million spanning 5 years