A novel stabilization mechanism for the type VI secretion system sheath

Abstract

The type VI secretion system (T6SS) is a phage-derived contractile nanomachine primarily involved in interbacterial competition. Its pivotal component, TssA, is indispensable for the assembly of the T6SS sheath structure, the contraction of which propels a payload of effector proteins into neighboring cells. Despite their key function, TssA proteins exhibit unexpected diversity and exist in two major forms, a short form (TssAS) and a long form (TssAL). While TssAL proteins interact with a partner, called TagA, to anchor the distal end of the extended sheath, the mechanism for the stabilization of TssAS-containing T6SSs remains unknown. Here we discover a class of structural components that interact with short TssA proteins and contribute to T6SS assembly by stabilizing the polymerizing sheath from the baseplate. We demonstrate that the presence of these components is important for full sheath extension and optimal firing. Moreover, we show that the pairing of each form of TssA with a different class of sheath stabilization proteins results in T6SS apparatuses that either reside in the cell for some time or fire immediately after sheath extension. We propose that this diversity in firing dynamics could contribute to the specialization of the T6SS to suit bacterial lifestyles in diverse environmental niches.

VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system

“…To determine how effectors contribute to T6SS assembly, we used pull-down analysis to test the interaction of effectors with the baseplate proteins TssE/F/G/K, as well as with the assembly chaperone TssA that interacts with multiple structural proteins [44][45][46][47][48]. All proteins were individually expressed in E. coli and cell lysates were mixed in pairs.…”

Presence and absence of type VI secretion systems in bacteria

“…Ready-to-use applications allow the screening of genomes for the presence of T6SS genes [15]. Comparative genomics has revealed homologies between different T6SS gene sequences and identified genes unique to particular T6SS subtypes (Box 1) [16].…”

The ecological impact of a bacterial weapon: microbial interactions and the Type VI secretion system

“… 2020a ; Bernal et al . 2021 ). Once the machinery has been assembled, with the sheath in an extended conformation, the T6SS undergoes a “firing” event, namely contraction of the sheath and expulsion of the puncturing structure through the membrane complex and out of the cell (Basler et al .…”