3.A.23.6.1
To interact with other cells, bacteria use contractile machines that function similarly to membrane-puncturing bacteriophages. The so-called type 6 secretion system (T6SS) functions from inside a bacterial cell. Böck et al. used modern electron microscopy methods and functional assays to resolve the structure and function of a T6SS in the cellular context. They identified three modules and showed large-scale structural changes upon firing. T6SSs are organized in multibarrel gun-like arrays and may contribute to the survival of bacteria inside their host.  Contractile injection systems (CISs) deliver effectors to mediate bacterial cell-cell interactions. Their structural components are homologous to the contractile tails of phages (1). CISs consist of an inner tube surrounded by a contractile sheath, a spike capping the inner tube, and a baseplate complex at the base of the sheath. Sheath contraction propels the inner tube into the target. Two modes of action divide CISs into “extracellular CISs” (eCISs) and “type 6 secretion” (T6S) systems (T6SSs). eCISs resemble headless phages; they are released into the medium and bind to the target cell surface. Examples are antibacterial R-type bacteriocins (Leiman and Shneider 2012), insecticidal antifeeding prophages (Afps) (Hurst et al. 2004), and metamorphosis-inducing structures (MACs) (Shikuma et al. 2014). By contrast, the T6SS is defined by its cytoplasmic localization and anchoring to the inner membrane (Basler et al. 2012; Hachani et al. 2016); Chang et al. 2017). Amoebophilus asiaticus is an obligate intracellular bacterial symbiont of amoebae. The Amoebophilus genome does not encode known secretion systems, but it contains a gene cluster with similarities to that of Afps. Böck et al. 2017 reasoned that the Afp-like gene cluster might encode a system that would give insight into T6SS structure, function, and evolution. Thus, the Amoebophilus Afp-like gene cluster encodes a T6SS (Böck et al. 2017). Sequence analyses indicated a close relationship to eCISs, and the term “T6SS subtype 4” (T6SS^iv) was therefore introduced. In contrast to the distant relationships of T6SS^i-iii to eCISs and phages that obstruct the reconstruction of an evolutionary path (1, 24), it can be hypothesized that T6SS^iv evolved from an Afp/MAC-like eCIS (independently of T6SS^i-iii) by the loss of tail fibers, loss of holin, and the establishment of interactions with the cytoplasmic membrane. Alternatively, T6SS^iv represents a primordial system from which eCISs, phages, and T6SS^i-iii evolved. T6SS^iv-like gene clusters were detected in six diverse bacterial phyla. The finding that diverse T6SS subtypes do not share a conserved gene set that would distinguish them from eCISs or phages emphasizes the necessity of an integrative approach to discover and characterize new systems. This situation is reminiscent of type IV secretion systems (3.A.7).  Bacterial communities have complex ecologies that require a range of interactions, whether to keep competitors at bay or to enter potential hosts or for predation. For these purposes, bacteria contain families of secretion systems that often work with contractile injection-like mechanisms to move effectors such as toxins or adhesins out of the cell and into specific target cells. Using cryo–electron microscopy structures and genetic analyses, Lien et al. 2024 found that an aquatic filamentous bacterium goes hunting armed with heptamers of a type 9 secretion system that act as grappling hooks to grab the flagella of prey and a type 6 secretion system effector that then stabs and kills it. Similar machinery may also be important in bacterial interactions closer to home, such as in the gut ecosystem.