Sequestration and asymmetric distribution of irreversibly oxidized proteins in Mtb

Carl Nathan, Julien Vaubourgeix and Gang Lin of Weill Cornell Medical College will test their hypothesis that tuberculosis is able to exit latency by distributing damaged proteins to a senescent cell lineage, while more functional proteins are diverted to a lineage with full replication potential. Regulating this post-latency cell division could be the target of new drugs. This project's Phase I research demonstrated that M. tuberculosis accumulates irreversibly oxidized proteins when its replication is blocked. These proteins form small aggregates that fuse into larger ones. One member of the progeny pair retains the aggregates when cell division resumes. In Phase II, the team will work to identify the genes that control this process for use in screens to find new and more powerful TB therapies.