Premium
New secreted toxins and immunity proteins encoded within the T ype VI secretion system gene cluster of S erratia marcescens
Author(s) -
English Grant,
Trunk Katharina,
Rao Vincenzo A.,
Srikannathasan Velupillai,
Hunter William N.,
Coulthurst Sarah J.
Publication year - 2012
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12028
Subject(s) - type vi secretion system , biology , microbiology and biotechnology , secretion , gene cluster , virulence , secretory protein , bacteria , gene , pathogen , genetics , biochemistry
Summary Protein secretion systems are critical to bacterial virulence and interactions with other organisms. The T ype 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 surprisingly elusive. Here, we identified two secreted substrates of the antibacterial T6SS from the opportunistic human pathogen, S erratia 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) included two specifically conferring self‐resistance (‘immunity’) against 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 Rap proteins were solved, revealing a novel helical fold, dependent on a structural disulphide bond, a structural feature consistent with their functional localization. Homologues of the S erratia 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 T6SS ‐secreted toxins. Molecular insight has been provided into how pathogens utilize antibacterial T6SSs to overcome competitors and succeed in polymicrobial niches.