Type 1 and 5 secretion systems and associated toxins - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 494

a C domain that contains a recognition site for a signal peptidase. On enter-
ing the periplasm the signal peptidase recognizes the uncharged residues at -1
and -3 relative to the cleavage site ( Hegde and Bernstein, 2006 ). A signifi-
cant subset of T5SS proteins (including members of types 5a, 5b, 5c, and 5e)
possess unusually long signal peptides, typically 50-60 residues long. The pur-
pose of the longer signal peptide has been studied for multiple proteins with
differing results; however the consensus view is that the extended peptide has
a subtle role, slowing translocation of the proteins across the inner membrane
to prevent accumulation of misfolded species in the periplasm. The precise
mechanism governing the decrease in translocation has yet to be elucidated
( Leyton et al., 2010, 2012 ).
On entering the periplasm, all further steps in the secretion pathway must be
independent of any energy input. Many OMPs have been shown to interact with
periplasmic chaperones such as SurA, Skp, and the bifuncational periplasmic
serine protease DegP. Many AT proteins also have been shown to interact with
these proteins ( Sklar et al., 2007; Baud et al., 2009; Knowles et al., 2009 ) sug-
gesting that T5SS biogenesis follows the same rules as normal OMPs, whereby
these chaperones mediate transit through the periplasm. Chaperones have also
been shown to be involved for the other T5SS subtypes, with DegP interacting
with the TPS protein FHA ( Baud et al., 2009 ), and Intimin shown to interact
with SurA, Skp, and DebP ( Bodelon et al., 2009 ). The role of chaperones is
currently unknown for TPS and TAA proteins. Thus, it seems that periplasmic
chaperones act specifically to keep the passenger domain in a translocation-
competent form and prevent aggregation and mis-folding ( Lazar and Kolter,
1996; Leyton et al., 2012 ).
In addition to chaperones, the β-barrel assembly machinery (Bam) com-
plex has been shown to be required for the biogenesis of many ATs ( Ieva and
Bernstein, 2009; Ruiz-Perez et al., 2009, 2010 ). The Bam complex is com-
prised of the integral β-barrel protein, BamA, and four peripheral lipopro-
teins, BamB-E ( Knowles et al., 2009 ). BamA and BamD have been shown
to be essential for the correct secretion of AT passenger domains across the
outer membrane, whereas BamB, C, and E are not required ( Rossiter et al.,
2011b ). However, redundant roles for BamB, C, and E have not been ruled out.
BamA consists of a large C-terminal β-barrel in the outer membrane and five
N-terminal POTRA domains that descend into the periplasm. POTRA 5 makes
direct contact with the lipoprotein BamD ( Kim et al., 2007 ), while POTRA 1
and 2 have been shown to bind peptides of OMPs ( Knowles et al., 2008 ) and
the chaperone SurA ( Bennion et al., 2010 ). As SurA interacts with BamA, it is
conceivable that ATs are delivered to the Bam complex by periplasmic chap-
erones. BamA has also been shown to be important for the secretion of pro-
teins belonging to other subgroups of T5SS, including the TPS CdiA/B ( Aoki
et al., 2008 ), the TAA YadA ( Lehr et al., 2010 ), and the type 5e secreted Intimin
( Bodelon et al., 2009 ). The role of BamD in TPS, TAA, and type 5e is yet to
be elucidated.