The type 2 secretion and type 4 pilus systems of Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 379

The gene products of the per operon, PerA, PerB, and PerC, directly augment
transcription of BFP genes ( Tobe et al., 1999 ) and of a second transcriptional
activator, Ler that in turn regulates additional EPEC genes involved in type 3
secretion (T3S) ( Elliott et al., 2000 ) (see Chapter 4). Additionally, BFP receptor
binding and retraction induce transient up-regulation of bfp transcription and
down-regulates expression of Ler-induced virulence genes ( Humphries et al.,
2010 ). Retraction of BFP fibers is also required for efficient translocation of
effector molecules secreted by this pathway ( Zahavi et al., 2011 ).
Bacterial stress response pathways play an important role in regulating the
expression of virulence factors in Gram-negative pathogens and the BFP is no
exception ( Nevesinjac and Raivio, 2005 ; MacRitchie et al., 2008 ; Vogt et al.,
2010 ; Lieberman et al., 2012 ). In the case of the BFP system, full activation of
the Cpx envelope stress response pathway represses transcription of BFP genes
and inhibits pilus expression ( Vogt et al., 2010 ). However, complete inactiva-
tion of the Cpx pathway in EPEC eliminates pilus biogenesis ( Nevesinjac and
Raivio, 2005 ) due to insufficient levels of periplasmic chaperone proteins such
as DegP, CpxP, and DsbA ( Vogt et al., 2010 ). A previous study revealed DsbA
was required for stability of bundlin and BFP biogenesis ( Zhang and Donnen-
berg, 1996 ). BFP can be expressed in K12 E. coli when the cloned bfp operon
is placed under control of a strong promoter ( Stone et al., 1996 ), but sufficient
BFP production to allow associated phenotypes requires constitutive activation
of Cpx ( Price and Raivio, 2009 ).
STRUCTURAL COMPONENTS OF T2S AND T4P MACHINES
Introduction
The T2S and T4P machines are structurally and functionally homologous ( Craig
et al., 2004 ; Ayers et al., 2009 ; Korotkov et al., 2012 ). These complexes can be
conceptualized as consisting of three distinct subcomplexes: the inner mem-
brane (IM) subassembly associated with at least one cytoplasmic ATPase; the
OM subassembly which consists of a transmembrane pore; and the translocated
substrate. Remarkably few differences between the T2S and T4P machines
account for their capacity to process very different substrates: the T2S extrudes
fully folded proteins likely driven through the pore by a pseudopilus while
the T4P system substrate is itself a pilus. Variations and accessory proteins do
exist and are discussed after the conserved components. All components are
listed using the General Secretory Pathway (Gsp) nomenclature used for ETEC
( Table 13.1 ).
The IM subassembly
The IM subassemblies of both the T2S and T4P machines consist of a core
set of homologous components, including several integral IM proteins and a
hexameric ATPase that provides the energy driving secretion ( Pelicic, 2008 ).