Type VII Secretion Systems

Jennifer HallLusubilo MalakbunguLSHTM-Medical Microbiology26th Oct, 2015

Introduction• Secretion systems have been grouped according to

mechanism, composition and evolutionary relationships• Type 1-6 basically known functioning in Gram negative

bacteria• Gram positive known to have one more specific system-

T7SS• T7SS composed of five systems, ESX1-ESX5• They are most noticeably found, in high levels, in the

capsule of mycobacteria• Related gene clusters are found in C.diptheriae and

Norcardia• They have also been found on S.aureus and are required

for virulence• S.scabies utilise them for sporulation

Structure• The high lipid content in the

mycobacterial cell wall/mycomembrane make it unique: T7SS is specialised• Proteins excreted usually as

heterodimers eg) ESX-A is conjugated to ESX-B as they are unstable independently• Y2H studies showed that, of the

multisubunit complex, Ecc B (Rv3871) interacts with ESX-B and delivers it to EccC (Rv3870) with ATP hydrolysis• Rv3870 passes the heterodimer on

to the secretary machinery

Protein & Substrates• ESX1, ESX3 and ESX5 are involved in

protein secretion. ESX3 also plays part in Iron acquisition.• ESX5-Transport PPE and PE-PGRS• ESX1 transports ESX-A and ESX-B • SUBSTRATES:-ESXA & ESXB (composed of Tryptophan & Glycine)-PE-PPE

Why do this?• 2011 5 types of mycobacterial T7SS had been

isolated• Those encoded by ESX-1 and ESX-5 have been

implicated in virulence• ESX-1 substrates make phagocytic membranes

leaky, eventually causing rupture and allowing escape into the cytosol

• Mutagenesis studies show that ESX-5 modulate cytokine responses in the bacteria favour by activating inflammasomes, intiating cell death and IL-1β release

• Both T7SS homologues contribute to bacterial spread and virulence

References• Abdallah AM et al., J of Immunol. 2011• Abdallah AM et al., Nat Rev Microbiol. 2007