The extracellular Contractile Injection Systems (eCIS) represent a novel class of relatively poorly characterized bacterial protein secretion and delivery devices. These protein nanomachines form phage tail-like contractile complexes. They were first recognized as insect toxin delivery systems in Serratia entomophila, which causes cessation of feeding and death of infected grass grub larvae (Hurst et al., 2004). Another eCIS device, termed as Photorhabdus Virulence Cassettes (PVCs), show potent injectable insecticidal activity against larvae of the wax moth (Yang et al., 2006). A more distantly related cousin of the eCIS devices was identified in the marine bacterium Pseudoalteromonas luteoviolacea. This system, designated Metamorphosis-Associated Contractile structure (MAC), triggers metamorphosis of the marine worm Hydroides elegans (Shikuma et al., 2014). A larger number of related yet uncharacterized and poorly annotated homologues of PVC/AFP operons were identified in the genomes of diverse Gram-negative, Gram-positive bacterial and archaeal genomes. These have previously been collectively defined as Phage-Like Translocation Structures (PLTS) (Sarris et al., 2014).
Visualization of PVC and AFP ultra-structures using transmission electron microscopy revealed they are morphologically similar to Pseudomonas aeruginosa R-type pyocins (Yang et al., 2006; Hurst et al., 2007). One issue confounding the reliable designation of novel eCIS loci is that they utilize homologues of certain subunits deployed by other bacterial contractile phage tail-like mechanisms, including bacteriophage, R-type pyocins and the Type VI secretion system (T6SS). For example, the AFP subunits Afp1 and Afp5 are very similar to tail tube protein subunit Gp19 of T4-like phages (Sen et al., 2010). In addition the Afp2, Afp3 and Afp4 subunits are not only homologous to one-another, but also share some similarity with the phage tail sheath protein FI (Hurst et al., 2004) and T6SS needle proteins (TssB/C). Other homologies that need to be taken into account include the similarity of the Afp8-like subunits to the T6SS (VgrG) and phage T4 (Gp5 and Gp27) cell-membrane puncturing spike proteins (Pukatzki et al., 2007; Silvermanet al., 2012) and a well-conserved AAA-ATPase subunit, Afp15 and TssH respectively. Moreover, we have been able to identify specific subunit proteins encoded by example eCIS loci- PVC/AFP that allow demarcation from other systems. These include Afp11, which contains a baseplate J-like domain, Afp14 and Afp16, which are believed to encode tape measure and cap proteins respectively.
It has been shown that the MAC devices are released by cell lysis, whereupon they form ordered outwardly facing arrays consisting of around 100 needle complexes with hexameric symmetry. Attachment of the H. elegans free-swimming larvae to this array triggers contraction of the needles and presumably injection of an effector, inducing metamorphosis to the sedentary adult form of the worm (Shikuma et al., 2014). This requires that the effector be loaded into the MAC prior to cell lysis and release. Likewise the AFP and PVC needle complexes are able to exert their toxic effects even when purified, again suggesting the effector proteins are pre-loaded into the needle complex before release.
Thus, despite sharing some genetic and morphological similarities to T6SSs and R-type pyocins, the PVC/AFP-like contractile injection systems actually represent a distinct mechanism that bacteria have evolved to mediate interactions with other organisms in their environment. T6SSs are also considered as one of contractile injection systems (CISs) as their structural components are homologous to the contractile tails of phages and anchoring to the inner membrane for cytoplasmic localization. By contrast, termed as "extracellular CISs" (eCISs), AFP, PVC and MAC, resemble headless phages and are released into the medium to bind the target cell surface.
About the database
Based on selected characteristics of functionally confirmed eCIS, we developed of a genomic context-based iterative approach for the large-scale identification of all potential eCIS loci in available bacterial genomes. With this approach, a phylogenetically diverse and broadly distributed superfamily of putative eCIS loci was identified from the 11,699 complete bacterial genomes with full annotations available from GenBank. The 631 eCIS loci cover both Gram-negative and Gram-positive bacteria, as well as Achaea. Therefore, dbeCIS, a dedicated database summarizing current information of these putative eCIS loci was constructed to facilitate future studies.
The database was produced from a collaborative project of
- National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College
- Lihong Chen, Bo Liu, Siyu Zhou, Dandan Zheng, Mingxin Chen, Jian Yang
- Beijing Friendship Hospital, Capital Medical University
- Nan Song, Nan Zhang, Yanyan Zhou, Guowei Yang
- Warwick Medical School, Warwick University
Lihong Chen,Nan Song,Bo Liu,Nan Zhang,Nabil-Fareed Alikhan,Zhemin Zhou,Yanyan Zhou,Siyu Zhou,Dandan Zheng,Mingxing Chen,Alexia Hapeshi,Joseph Healey,Nicholas R. Waterfield,Jian Yang,Guowei Yang, 2019. Genome-wide Identification and Characterization of a Superfamily of Bacterial Extracellular Contractile Injection Systems. Cell Reports 29(2):511-521.
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