Type VI secretion system effectors: poisons with a purpose

Abstract

The type VI secretion system (T6SS) mediates interactions between a broad range of Gram-negative bacterial species. Recent studies have led to a substantial increase in the number of characterized T6SS effector proteins and a more complete and nuanced view of the adaptive importance of the system. Although the T6SS is most often implicated in antagonism, in this Review, we consider the case for its involvement in both antagonistic and non-antagonistic behaviours. Clarifying the roles that type VI secretion has in microbial communities will contribute to broader efforts to understand the importance of microbial interactions in maintaining human and environmental health, and will inform efforts to manipulate these interactions for therapeutic or environmental benefit.

Figure 1. T6SS effectors target varying aspects of bacterial physiology

Localization and activity of interbacterial T6S effectors delivered by an attacking donor cell (red) to a recipient cell (green) via the T6S apparatus (grey tube). Effector targets include nucleic acids, the peptidoglycan cell wall (PG), the inner-membrane (IM), and the outer-membrane (OM). Precise enzymatic specificity, where known, is further indicated within numbered panels. Parentheses indicate enzymatic activities predicted from structure-function and/or nonspecific enzymatic analyses that have yet to be biochemically confirmed. Distribution denotes effector presence within the different proteobacterial classes ( , , , , or ). Group refers to the number of evolutionarily distinct families of effector proteins within an enzymatic class, and number to the unique instances of homologs within those groups. Numbers presented are limited to those reported in the literature; groups and numbers are provided only when a systematic effort has been made to characterize a class of effectors^–,,,,,,,. Dashes indicate a lack of available published data. Abbreviations: M, N-acetylmuramic acid, G, N-acetylglucosamine, mDAP, meso-diaminopimelic acid.

Figure 2. Multiple roles for interbacterial T6S

Potential activities of T6S within an established bacterial community, both antagonistic (between red and blue competitor cells) and non-antagonistic (between two blue cells). Dashed outlines indicate cells experiencing T6-mediated toxicity, a lack of an outline indicates a cell lysing due to the activity of T6SS effectors. Arrows represent the directionality of T6S interactions.

Figure 3. Interbacterial T6S and infection

Potential roles for T6S-mediated interactions in disease. Both antagonistic and alternative functions for T6S are depicted. The T6SS appears as an additional structure on cells; it is orange when mediating an antagonistic function, and blue when its activity has an alternative function. Cells being attacked by the T6SS of others are depicted with a dashed outline. Stripes across a cell indicate T6S-mediated change in physiology, and a yellow halo around a cell depicts intracellular contents released upon lysis. In the intestine, T6S might be used by invading pathogens (intestine close-up, left) or by commensals blocking invasion (intestine close-up, right). In skin wounds T6S could be important for competition during colonization (wound closeup, blue vs. green cells), could allow established populations to protect their niche from susceptible invaders (wound close-up, red vs. green cells), or could facilitate signaling within populations (red cell targeting another red cell). In chronic lung infections, roles for T6S could include preventing invasion of an established population by susceptible species (lung cross-section, upper right), facilitating invasion of a susceptible established population (lung cross-section, bottom), or contributing to aggregate structure by mediating the lysis of a subpopulation of cells (lung cross section, upper left).