Type 3 secretion systems - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 423

Once the needle is assembled, the tip and translocon components (mid
effectors) must be secreted prior to secretion of the late effectors and a second
substrate specificity switch is believed to control this transition. Several such
negative regulatory controls have been described, some of which bind to the tip
and physically block secretion while some act at the base of the injectisome.
A family of proteins with shared but remote sequence similarity (SepD:SepL
complex in EPEC, MxiC in Shigella , YopN:TyeA complex in Yersinia ) have
been shown to regulate translocator secretion ( O'Connell et al., 2004 ; Deng
et al., 2005 ; Hamad and Nilles, 2007 ; Deane et al., 2008b ). It is thought that these
proteins act as gatekeepers, allowing the secretion of translocon components but
restricting the secretion of late effectors until an appropriate signal is detected
and the secretion blockade relieved. The nature of this signal varies from species
to species with environmental factors such as pH, temperature, small molecules
and host cell contact demonstrated to trigger secretion in different systems.
Additionally, in a recent elegant study, Galan and colleagues described a sort-
ing platform capable of ensuring secretion of the translocases prior to the late
effectors ( Lara-Tejero et al., 2011 ). This high-molecular-weight cytoplasmic
complex was composed of three proteins - SpaO (the Salmonella typhimurium
C-ring protein; SepQ/EscQ in EPEC), OrgA (Orf4 in EPEC) and OrgB
(the ATPase peripheral stalk homolog; EscL in EPEC) - and was able to recog-
nize the chaperones for both the mid and late effectors, delivering their complexes
to the injectisome prior to secretion in an ATPase-dependent manner. It was found
that the sorting platform had a higher affinity for the translocase chaperones
ensuring the selective and ordered secretion. Importantly, similar complexes have
been described in EPEC ( Biemans-Oldehinkel et al., 2011 ) and Shigella ( Johnson
and Blocker, 2008 ) suggesting this may be a common means of regulation.
REGULATION OF TYPE 3 SECRETION
Type 3 secretion is a tightly regulated process; indeed, several pathogens (such
as Salmonella typhimurium ( Srikanth et al., 2011 ) and Burkholderia species
( Sun and Gan, 2010 )) possess several T3SSs, which are activated at different
times during the course of infection. In practice, the secretion of a certain set of
effectors is induced at one stage of the infection, and stopped at a later stage.
Strikingly, it has been shown that induction of the Salmonella SPI-1 T3SS
( Sturm et al., 2011 ) or Yersinia spp. T3SS ( Brubaker and Surgalla, 1964 ; Wiley
et al., 2007 ) leads to a heavy penalty in bacterial growth, illustrating the burden
that unregulated type 3 secretion would cause on bacteria.
Environmental regulation
One common aspect of type 3 secretion regulation is the observation that it is
induced upon contact with the cell of an infected organism ( Cornelis, 2000 ). The
molecular detail of eukaryotic cell sensing remains unknown to date; however,