Sensing of intracellular Hcp levels controls T6SS expression in Vibrio cholerae

Significance Assembly, firing, and recycling of the type 6 secretion system (T6SS) organelle is a costly process as each secretion event ejects hundreds of inner-tube Hcp molecules. In comparison to bacteria whose T6SSs are tightly regulated, bacterial strains that constitutively display T6SS activity would seem inefficient in their deployment of T6SS, especially if secretion is interrupted by environmental conditions that reduce available cellular energy. Here we have discovered a quantity-sensing feedback control that avoids wasteful accumulation of secreted proteins in several pathogens that express the T6SS. By sensing the efficiency of secretion of its major substrate (Hcp), this regulatory mechanism likely conserves energy and would therefore be helpful in responding to a variety of stress conditions that interrupt T6SS secretion.