New secreted toxins and immunity proteins encoded within the type VI secretion system gene cluster of Serratia marcescens

Grant English, Katharina Trunk, Vincenzo A. Rao, Velupillai Srikannathasan, William N. Hunter, Sarah J. Coulthurst (Lead / Corresponding author)

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    99 Citations (Scopus)


    Protein secretion systems are critical to bacterial virulence and interactions with other organisms. The Type VI secretion system (T6SS) is found in many bacterial species and is used to target either eukaryotic cells or competitor bacteria. However, T6SS-secreted proteins have proven surprisinglyelusive. Here, we identified two secreted subcluded two specifically conferring self-resistance ('immunity') agstrates of the antibacterial T6SS from the opportunistichuman pathogen, Serratia marcescens. Ssp1 and Ssp2, both encoded within the T6SS gene cluster, were confirmed as antibacterial toxins delivered by the T6SS. Four related proteins encoded around the Ssp proteins ('Rap' proteins) inainst T6SS-dependent Ssp1 or Ssp2 toxicity. Biochemical characterization revealed specific, tight binding between cognate Ssp-Rap pairs, forming complexes of 2:2 stoichiometry. The atomic structures of two Rapproteins were solved, revealing a novel helical fold, dependent on a structural disulphide bond, a structural feature consistent with their functional localization. Homologues of the Serratia Ssp and Rap proteins are found encoded together within other T6SS gene clusters, thus they represent founder members of new families of T6SS-secreted and cognate immunity proteins. We suggest that Ssp proteins are the original substrates of the S. marcescens T6SS, before horizontal acquisition of other T6SSsecreted toxins. Molecular insight has been providedinto how pathogens utilize antibacterial T6SSs to overcome competitors and succeed in polymicrobial niches.
    Original languageEnglish
    Pages (from-to)921-936
    Number of pages16
    JournalMolecular Microbiology
    Issue number4
    Publication statusPublished - Nov 2012


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