Professor Laura Dassama of Stanford University

"Deciphering the molecular mechanisms of lipid trafficking in bacteria"

Lipids, including sterols, are important for mammalian cell physiology. These molecules form part of membranes and modulate their fluidity, thereby maintaining membrane integrity, providing tolerance to stress, promoting fusion events, etc. Whereas decades of research have provided molecular insights into eukaryotic sterol lipid synthesis, transport, regulation, and function, a similar understanding of sterols is lacking for bacteria. It is known that some bacteria make sterols de novo, and others use it to establish pathogenesis. Moreover, gut microbiota interactions with sterols can alter host lipid metabolism and profoundly impact human health. Despite the preponderance of research about microbial interactions with these lipids, missing are molecular insights into how the interactions occur and how they are regulated. We begin to address this knowledge gap by identifying the first examples of transporters for bacterial sterols. We provide structures and molecular mechanisms for these proteins and note that they differ substantially from eukaryotic sterol transporters. The widespread presence of homologs in bacterial genomes suggests that sterol trafficking is not as rare as once thought. Guided by structural insights, we now aim to uncover the molecular details that govern bacterial engagement with sterol lipids, which we posit will reveal novel targets for therapeutic interventions in bacterial colonization and aberrant sterol metabolism.