Phase separation and clustering of an ABC transporter in <i>Mycobacterium tuberculosis</i>

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 from Mycobacterium 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 in Mtb . Our findings suggest that phase separation can play a key role in the regulation of clustering and activity of membrane-bound bacterial proteins. </jats:p