The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins

Geller, Alexander Martin; Pollin, Inbal; Zlotkin, David; Danov, Aleks; Nachmias, Nimrod; Andreopoulos, William; Shemesh, Keren; Levy, Asaf

doi:10.1038/s41467-021-23777-7

Cited by 40 publications

(59 citation statements)

References 80 publications

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“…Classical T6SSs (subtypes i – iii) and R-type pyocins (eCISs) form relatively homogeneous groups of CISs. Recent bioinformatic analyses revealed an additional phylogenetic group of CISs with high abundance and diversity 16 – 19 . This group comprises hundreds of putative CIS gene clusters, with only a few of them being studied so far.…”

Section: Mainmentioning

confidence: 99%

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Identification and structure of an extracellular contractile injection system from the marine bacterium Algoriphagus machipongonensis

Ericson

Lien

et al. 2022

Nat Microbiol

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Contractile injection systems (CISs) are phage tail-like nanomachines, mediating bacterial cell–cell interactions as either type VI secretion systems (T6SSs) or extracellular CISs (eCISs). Bioinformatic studies uncovered a phylogenetic group of hundreds of putative CIS gene clusters that are highly diverse and widespread; however, only four systems have been characterized. Here we studied a putative CIS gene cluster in the marine bacterium Algoriphagus machipongonensis. Using an integrative approach, we show that the system is compatible with an eCIS mode of action. Our cryo-electron microscopy structure revealed several features that differ from those seen in other CISs: a ‘cap adaptor’ located at the distal end, a ‘plug’ exposed to the tube lumen, and a ‘cage’ formed by massive extensions of the baseplate. These elements are conserved in other CISs, and our genetic tools identified that they are required for assembly, cargo loading and function. Furthermore, our atomic model highlights specific evolutionary hotspots and will serve as a framework for understanding and re−engineering CISs.

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Section: Mainmentioning

confidence: 99%

“…This strain was previously co-isolated with the choanoflagellate Salpingoeca rosetta 26 and was shown to induce the formation of multicellular colonies (rosettes) of S. rosetta 27 – 29 . Bioinformatic analyses showed that ~69% of bacteria in the Algoriphagus genus harbour a putative CIS gene cluster 19 .…”

Section: Mainmentioning

confidence: 99%

Identification and structure of an extracellular contractile injection system from the marine bacterium Algoriphagus machipongonensis

Ericson

Lien

et al. 2022

Nat Microbiol

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“…Several similar so-called chaperones are also found in T4SS, although their functions are not well established ( 40 – 42 ). In the field of T6SS, which have great structure similarities with PVC and other eCIS complexes ( 43 ), several types of mechanisms have been determined in assisting the effector secretion. Tec (DUF4123) family proteins displayed essential roles for T6SS-dependent loading of the effectors ( 44 ); Eag (DUF1795) family proteins engaged in stabilizing effectors and promoting T6SS delivery through the spike ( 45 , 46 ); and a DUF2169 or DUF2875 protein has also been described as a chaperone or adaptor for T6SS substrates delivery ( 47 , 48 ).…”

Section: Discussionmentioning

confidence: 99%

N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system

et al. 2022

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Extracellular contractile injection systems (eCISs) are widespread bacterial nanomachines that resemble T4 phage tail. As a typical eCIS, Photorhabdus virulence cassette (PVC) was proposed to inject toxins into eukaryotic cells by puncturing the cell membrane from outside. This makes it an ideal tool for protein delivery in biomedical research. However, how to manipulate this nanocomplex as a molecular syringe is still undetermined. Here, we identify that one group of N-terminal signal peptide (SP) sequences are crucial for the effector loading into the inner tube of PVC complex. By application of genetic operation, cryo–electron microscopy, in vitro translocation assays, and animal experiments, we show that, under the guidance of the SP, numerous prokaryotic and eukaryotic proteins can be loaded into PVC to exert their functions across cell membranes. We therefore might customize PVC as a potent protein delivery nanosyringe for biotherapy by selecting cargo proteins in a broad spectrum, regardless of their species, sizes, and charges.

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“…Another member of this group, found in a symbiont of amoebae, assembles bundles of T6SSs that mediate interactions with host membranes 15 . Importantly, recent bioinformatic searches detected related gene clusters in hundreds of diverse bacterial and even archaeal genomes 11 , 15 – 17 .…”

Section: Mainmentioning

confidence: 99%

Structure of a thylakoid-anchored contractile injection system in multicellular cyanobacteria

et al. 2022

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Contractile injection systems (CISs) mediate cell–cell interactions by phage tail-like structures, using two distinct modes of action: extracellular CISs are released into the medium, while type 6 secretion systems (T6SSs) are attached to the cytoplasmic membrane and function upon cell–cell contact. Here, we characterized a CIS in the multicellular cyanobacterium Anabaena, with features distinct from extracellular CISs and T6SSs. Cryo-electron tomography of focused ion beam-milled cells revealed that CISs were anchored in thylakoid membrane stacks, facing the cell periphery. Single particle cryo-electron microscopy showed that this unique in situ localization was mediated by extensions of tail fibre and baseplate components. On stress, cyanobacteria induced the formation of ghost cells, presenting thylakoid-anchored CISs to the environment. Functional assays suggest that these CISs may mediate ghost cell formation and/or interactions of ghost cells with other organisms. Collectively, these data provide a framework for understanding the evolutionary re-engineering of CISs and potential roles of these CISs in cyanobacterial programmed cell death.

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The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins

Cited by 40 publications

References 80 publications

Identification and structure of an extracellular contractile injection system from the marine bacterium Algoriphagus machipongonensis

Identification and structure of an extracellular contractile injection system from the marine bacterium Algoriphagus machipongonensis

N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system

Structure of a thylakoid-anchored contractile injection system in multicellular cyanobacteria

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