Phase separation and clustering of an ABC transporter in Mycobacterium tuberculosis

Significance Nanoclustering has emerged as an organization principle of membrane proteins. This form of compartmentalization has been observed in eukaryotes and, to a lesser extent, in bacteria. Bacterial membrane proteins in secretion systems often play central roles during host invasion. Here we reveal that an ABC transporter fromMycobacterium tuberculosis (Mtb ), which is important for its growth in mice, compartmentalizes in the bacterial membrane. We demonstrate that the cytoplasmic region of this transporter has an intrinsic ability to phase-separate into mesoscale assemblies, and that this process is controllable via the action of the signal-integrating serine/threonine protein kinases and phosphatase inMtb . Our findings suggest that phase separation can play a key role in the regulation of clustering and activity of membrane-bound bacterial proteins.