Functional diversity of accessory factors of the type VI secretion system

The type VI secretion system (T6SS) is a nanomachine utilized by Gram-negative bacteria to secrete toxic effectors. The T6SS is employed against both prokaryotic and eukaryotic targets, allowing for competitive advantage and virulence of the attackers in a wide variety of environments. Recent work has revealed the great diversity of T6SS systems. Beyond the canonical, conserved architectural genes of the T6SS, diverse T6SS-associated genes (TAGs) are employed to optimize T6SS activity, compensate for variations in architecture, and dictate T6SS use. Although various TAGs have been discovered in T6SS gene clusters, they display unique activities in modifying their cognate T6SS. In this review, we discuss several of the better-studied TAGs, as well as highlight under-researched TAGs that are likely of great significance. As a means to better understand TAG roles, identify common principles and unifying themes, we present the following six functional categories: Firing Coordinators, Target Recognition Factors, Structural Factors, Transcriptional Regulators, Secretion Regulators, and Unknown TAGs.