Scientists have known for decades that the virulence of many strains of pathogenic bacteria can be correlated with colony morphology. Koch observed more than 100 years ago that the virulence of Mycobacterium tuberculosis (Mtb) is correlated with the formation of braided microscopic bundles, known as ‘cording’ (visualized by auramine rhodamine fluorescent stain in picture). Bacterial colony structure is determined by cell wall components, but detailed studies of this complex mixture of lipids and glycolipids in Mtb have been limited by a lack of cell surface mutants. Recent advances in Mtb genetics, along with the completion of its genome sequence, have allowed researchers to genetically screen mutants with altered colony morphologies and investigate the involvement of the cell envelope in mycobacterial virulence. In the April issue of Molecular Cell, Glickman et al. reported the identification of a mycobacterial gene, pcaA, that is required for cording and persistent infection. PcaA is a cyclopropane synthase involved in the formation of mycolic acids, modified membrane lipids found in many bacterial species. The authors found that pcaA mutant bacteria initially replicated normally in vivo, but failed to persist within and kill infected mice, indicating that cyclopropanated lipids are required for latent Mtb infections. Mice infected with the pcaA mutant strain did not experience severe pulmonary damage, and had alterations in the composition of inflammatory cell infiltration compared with that of mice infected with wild-type Mtb. “Studies of this type are revealing that lipid and glycolipid molecules are important determinants of Mtb pathogenesis—some lipids are important for initial in vivo replication in the organism, while others are important for long-term persistence,” explained Glickman. The authors plan to better characterize the immune response to pcaA and to test the pcaA mutant in formal models of Mtb latency, a condition that affects approximately 32% of the world's population. As cyclopropanated lipids do not exist in humans, pcaA may also make a good drug target.