Newcastle University, UK
The Staphylococcus aureus type VII protein secretion system
Meeting ID: 882 8222 0898
Dear Journal Club members,
We are honored to continues with great speakers and host Tracy Palmer, Prof. of Microbiology from Newcastle University, UK
The Staphylococcus aureus Type VII protein secretionsystem
Tracy Palmer,Newcastle University.
The TypeVII protein secretion system (T7SS) is found in many Gram-positive bacteriaincluding the human pathogen Staphylococcusaureus. S. aureus encodes asingle T7SS that is required for virulence in mouse models of infection. The S. aureus T7SS machinery is composed offour membrane proteins, EsaA, EssA, EssB and EssC, and two additional globularproteins EsxA and EsaB. Structural studies suggest that EssC, a member of theAAA+ ATPase superfamily, protein most likely forms the secretion pore. Strainsof S. aureus show sequencevariability in the most C-terminal ATPase domain of EssC and evidence suggeststhat this region of the protein is involved in substrate recognition.
Somestrains of S. aureus secrete a largenuclease toxin through the T7SS that is very potent, and highly active againstchromosomal DNA. S. aureus protectsitself from the action of the nuclease by producing an anti-toxin that bindstightly to the nuclease, blocking its activity. The nuclease also interactswith a specific chaperone that appears to target the nuclease-anti-toxincomplex to the secretion machinery. During secretion by the T7SS, theanti-toxin is probably dissociated from the nuclease and remains inside thecell while the nuclease is secreted. Co-culture experiments indicates that theT7-dependent nuclease mediates competition between closely related S. aureus strains, which is likely to beimportant during colonization.
Morerecently we have identified a further T7 substrate protein that encoded acrossall S. aureus strains as well as in Listeria and Enterococci. The protein has a toxic C-terminal domain that depolarizesthe bacterial cytoplasmic membrane. Toxic activity is prevented by interactionwith a membrane-bound anti-toxin. Using a zebrafish hindbrain ventricleinfection model, we demonstrate that this T7 substrate protein is required forfull virulence.