Nooks and crannies in type VI secretion regulation

Abstract

Type VI secretion systems (T6SS) are macromolecular, transenvelope machines encoded within the genomes of most Gram-negative bacteria, including plant, animal, and human pathogens, as well as soil and environmental isolates. T6SS are involved in a broad variety of functions: from pathogenesis to biofilm formation and stress sensing. This large array of functions is reflected by a vast diversity of regulatory mechanisms: repression by histone-like proteins and regulation by quorum sensing, transcriptional factors, two-component systems, alternative sigma factors, or small regulatory RNAs. Finally, T6SS may be produced in an inactive state and are turned on through the action of a posttranslational cascade involving phosphorylation and subunit recruitment. The current data reviewed here highlight how T6SS have been integrated into existing regulatory networks and how the expression of the T6SS loci is precisely modulated to adapt T6SS production to the specific needs of individual bacteria.

FIG. 1.

Regulation of the P. aeruginosa T6SS loci. The various regulatory pathways involved in the regulation of P. aeruginosa HSI-1, HSI-2, and HSI-3 T6SS clusters are indicated. Effects of induction (green arrows) and repression (red bars) are shown. The predicted σ⁵⁴-dependent regulation suggested by in silico analyses is depicted. The signal(s) that leads to LadS or RetS activation is unknown and is thus represented by a question mark.

FIG. 2.

Regulation of the FPI T6SS locus. Expression of the locus is dictated through RNA polymerase recruitment by the phosphorylated PmrA protein and the MglA/SspA/PigR complex. The form of PigR activated by the stringent response through the alarmone ppGpp is indicated by an asterisk. The signal that leads to KdpD-dependent PmrA phosphorylation (?) is unknown.

FIG. 3.

Posttranslational regulation. PpkA dimerization induced by the TagR protein leads to FHA protein phosphorylation and subsequent recruitment of essential components of the secretion apparatus. PpkA activity is antagonized by the activity of the PppA phosphatase. Mechanisms of activation (green arrows) and inhibition (red bars) are indicated. The asterisk denotes activated FHA protein.